p.Asp639Asn in exon 12 of TSPEAR: This variant is not expected to have clinical significance because it has been identified in 0.5% (214/39556) of European chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs138480801).
ClinVar Genomic variation as it relates to human health
NM_144991.3(TSPEAR):c.1915G>A (p.Asp639Asn)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(16)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Conflicting classifications of pathogenicity
Pathogenic(1); Likely pathogenic(2); Uncertain significance(3); Benign(2); Likely benign(2)
Pathogenic(1); Likely pathogenic(2); Uncertain significance(3); Benign(2); Likely benign(2)
16
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_144991.3(TSPEAR):c.1915G>A (p.Asp639Asn)
Variation ID: 227135 Accession: VCV000227135.45
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 21q22.3 21: 44499878 (GRCh38) [ NCBI UCSC ] 21: 45919761 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 9, 2018 Nov 24, 2024 Sep 20, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_144991.3:c.1915G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_659428.2:p.Asp639Asn missense NM_001272037.2:c.1711G>A NP_001258966.1:p.Asp571Asn missense NC_000021.9:g.44499878C>T NC_000021.8:g.45919761C>T NG_033806.1:g.216701G>A - Protein change
- D639N, D571N
- Other names
- -
- Canonical SPDI
- NC_000021.9:44499877:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00040 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 0.00040
1000 Genomes Project 30x 0.00047
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00223
The Genome Aggregation Database (gnomAD), exomes 0.00229
Trans-Omics for Precision Medicine (TOPMed) 0.00239
The Genome Aggregation Database (gnomAD) 0.00244
Exome Aggregation Consortium (ExAC) 0.00345
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| TSPEAR | - | - |
GRCh38 GRCh37 |
418 | 1017 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Benign (1) |
criteria provided, single submitter
|
Jan 7, 2016 | RCV000218316.7 | |
| Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
|
Sep 20, 2024 | RCV000721121.8 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 18, 2018 | RCV001335431.2 | |
| Conflicting interpretations of pathogenicity (6) |
criteria provided, conflicting classifications
|
Apr 1, 2024 | RCV000844249.31 | |
|
TSPEAR-related disorder
|
Likely benign (1) |
no assertion criteria provided
|
Aug 24, 2020 | RCV003977608.2 |
| Uncertain significance (1) |
criteria provided, single submitter
|
Aug 16, 2018 | RCV001267478.3 | |
| Conflicting interpretations of pathogenicity (2) |
no assertion criteria provided
|
Nov 24, 2023 | RCV002470820.4 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Benign
(Jan 07, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000269929.3
First in ClinVar: May 29, 2016 Last updated: Aug 26, 2019 |
Comment:
p.Asp639Asn in exon 12 of TSPEAR: This variant is not expected to have clinical significance because it has been identified in 0.5% (214/39556) of European … (more)
p.Asp639Asn in exon 12 of TSPEAR: This variant is not expected to have clinical significance because it has been identified in 0.5% (214/39556) of European chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs138480801). (less)
Number of individuals with the variant: 2
|
|
|
Benign
(Aug 06, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV001146262.1
First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020 |
|
|
|
Uncertain significance
(Jan 18, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive nonsyndromic hearing loss 98
Affected status: yes
Allele origin:
paternal
|
Baylor Genetics
Accession: SCV001528581.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
|
|
|
Uncertain significance
(Aug 16, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: yes
Allele origin:
germline
|
Ambry Genetics
Accession: SCV001445659.2
First in ClinVar: Nov 21, 2020 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Clinical Features:
Recurrent upper respiratory tract infections (present) , Oligodontia of primary teeth (present) , Fatigue (present) , Hernia (present) , Leukopenia (present) , Anhidrosis (present) , … (more)
Recurrent upper respiratory tract infections (present) , Oligodontia of primary teeth (present) , Fatigue (present) , Hernia (present) , Leukopenia (present) , Anhidrosis (present) , Epistaxis (present) , Oligodontia (present) , Pancytopenia (present) , Thrombocytopenia (present) , Dry skin (present) , Asthma (present) , Sparse hair (present) , Delayed speech and language development (present) , Abnormality of dental morphology (present) , Hypotrichosis (present) , Abnormal bleeding (present) , Abnormality of the vasculature (present) (less)
Sex: male
Ethnicity/Population group: Caucasian
|
|
|
Likely pathogenic
(Apr 20, 2023)
|
criteria provided, single submitter
Method: research
|
Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis
Affected status: yes
Allele origin:
paternal
|
Duke University Health System Sequencing Clinic, Duke University Health System
Accession: SCV003919029.1
First in ClinVar: Apr 30, 2023 Last updated: Apr 30, 2023 |
|
|
|
Likely benign
(Jan 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001035626.6
First in ClinVar: Dec 16, 2019 Last updated: Feb 20, 2024 |
|
|
|
Pathogenic
(Apr 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000986296.9
First in ClinVar: Aug 26, 2019 Last updated: Sep 29, 2024 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30046887, … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30046887, 27736875, 34042254, 25855803, 33144682, 37853563, 37009414) (less)
|
|
|
Likely benign
(Mar 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004146670.10
First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024 |
Comment:
TSPEAR: BS2
Number of individuals with the variant: 1
|
|
|
Likely Pathogenic
(Aug 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center
Accession: SCV005397471.1
First in ClinVar: Nov 17, 2024 Last updated: Nov 17, 2024 |
Comment:
This sequence variant is a single nucleotide substitution (G>A) at coding nucleotide 1915 in the TSPEAR gene which results in an aspartic acid to asparagine … (more)
This sequence variant is a single nucleotide substitution (G>A) at coding nucleotide 1915 in the TSPEAR gene which results in an aspartic acid to asparagine amino acid change at residue 639 in the TSPEAR protein. This is a previously reported variant (ClinVar) which has been reported with a second variant in compound heterozygous state in multiple individuals with ectodermal dysplasia with tooth agenesis (PMID: 34042254, 27736875). The variant is present in 594/263832 alleles, including 1 homozygote, in the gnomAD control population dataset. Multiple bioinformatic tools predict that this variant is likely to be damaging, and aspartic acid is highly conserved at this protein position in vertebrates. Functiol studies testing the effects of this variant have not been performed, to our knowledge. Based on the available evidence, we consider this variant to be likely pathogenic; however, based on the presence of a homozygous individual in a control dataset, it may represent an allele which requires a stronger loss of function allele on the opposite chromosome for disease phenotypes to manifest. ACMG Criteria: PM3, PP3, PP4, PS4 (less)
|
|
|
Uncertain significance
(Sep 20, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV005086110.2
First in ClinVar: Jul 23, 2024 Last updated: Nov 24, 2024 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with tooth agenesis, selective, 10 (MIM#620173) and ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis (MIM#618180). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from aspartic acid to asparagine. (I) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (592 heterozygotes, 1 homozygote). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been classified as benign, likely benign, a VUS and pathogenic by clinical laboratories in ClinVar. The variant has also been observed as compound heterozygous or homozygous in eight families with hypodontia and ectodermal dysplasia in the literature, and was classified as a VUS or as likely pathogenic (PMID: 34042254, 27736875, 37009414). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
|
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001963134.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001971025.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
|
Pathogenic
(Dec 05, 2022)
|
no assertion criteria provided
Method: literature only
|
ECTODERMAL DYSPLASIA 14, HAIR/TOOTH TYPE, WITHOUT HYPOHIDROSIS
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000852003.2
First in ClinVar: Nov 10, 2018 Last updated: Dec 11, 2022 |
Comment on evidence:
For discussion of the c.1915G-A transition in the TSPEAR gene, resulting in an asp639-to-asn (D639N) substitution, that was found in compound heterozygous state in a … (more)
For discussion of the c.1915G-A transition in the TSPEAR gene, resulting in an asp639-to-asn (D639N) substitution, that was found in compound heterozygous state in a female patient (family C) with ectodermal dysplasia-14, hair/tooth type (ECTD14; 618180), by Peled et al. (2016), see 612920.0003. (less)
|
|
|
Pathogenic
(Dec 20, 2022)
|
no assertion criteria provided
Method: literature only
|
TOOTH AGENESIS, SELECTIVE, 10
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV002769559.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment on evidence:
For discussion of the c.1915G-A transition (c.1915G-A, NM_144991.2) in exon 12 of the TSPEAR gene, resulting in an asp639-to-asn (D639N) substitution, that was found in … (more)
For discussion of the c.1915G-A transition (c.1915G-A, NM_144991.2) in exon 12 of the TSPEAR gene, resulting in an asp639-to-asn (D639N) substitution, that was found in compound heterozygous state in a 9-year-old boy of European ancestry (subject 17) with nonsyndromic oligodontia (STHAG10; 620173) by Bowles et al. (2021), see 612920.0012. (less)
|
|
|
Uncertain significance
(Nov 24, 2023)
|
no assertion criteria provided
Method: clinical testing
|
Tooth agenesis, selective, 10
Affected status: yes
Allele origin:
germline
|
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas
Accession: SCV004171618.1
First in ClinVar: Dec 02, 2023 Last updated: Dec 02, 2023 |
|
|
|
Likely benign
(Aug 24, 2020)
|
no assertion criteria provided
Method: clinical testing
|
TSPEAR-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004792731.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30046887, 27736875, 34042254, 25855803, 33144682, 37853563, 37009414)
Comment:
TSPEAR: BS2
Comment:
This sequence variant is a single nucleotide substitution (G>A) at coding nucleotide 1915 in the TSPEAR gene which results in an aspartic acid to asparagine amino acid change at residue 639 in the TSPEAR protein. This is a previously reported variant (ClinVar) which has been reported with a second variant in compound heterozygous state in multiple individuals with ectodermal dysplasia with tooth agenesis (PMID: 34042254, 27736875). The variant is present in 594/263832 alleles, including 1 homozygote, in the gnomAD control population dataset. Multiple bioinformatic tools predict that this variant is likely to be damaging, and aspartic acid is highly conserved at this protein position in vertebrates. Functiol studies testing the effects of this variant have not been performed, to our knowledge. Based on the available evidence, we consider this variant to be likely pathogenic; however, based on the presence of a homozygous individual in a control dataset, it may represent an allele which requires a stronger loss of function allele on the opposite chromosome for disease phenotypes to manifest. ACMG Criteria: PM3, PP3, PP4, PS4
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with tooth agenesis, selective, 10 (MIM#620173) and ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis (MIM#618180). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from aspartic acid to asparagine. (I) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (592 heterozygotes, 1 homozygote). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been classified as benign, likely benign, a VUS and pathogenic by clinical laboratories in ClinVar. The variant has also been observed as compound heterozygous or homozygous in eight families with hypodontia and ectodermal dysplasia in the literature, and was classified as a VUS or as likely pathogenic (PMID: 34042254, 27736875, 37009414). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
p.Asp639Asn in exon 12 of TSPEAR: This variant is not expected to have clinical significance because it has been identified in 0.5% (214/39556) of European chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs138480801).
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30046887, 27736875, 34042254, 25855803, 33144682, 37853563, 37009414)
Comment:
TSPEAR: BS2
Comment:
This sequence variant is a single nucleotide substitution (G>A) at coding nucleotide 1915 in the TSPEAR gene which results in an aspartic acid to asparagine amino acid change at residue 639 in the TSPEAR protein. This is a previously reported variant (ClinVar) which has been reported with a second variant in compound heterozygous state in multiple individuals with ectodermal dysplasia with tooth agenesis (PMID: 34042254, 27736875). The variant is present in 594/263832 alleles, including 1 homozygote, in the gnomAD control population dataset. Multiple bioinformatic tools predict that this variant is likely to be damaging, and aspartic acid is highly conserved at this protein position in vertebrates. Functiol studies testing the effects of this variant have not been performed, to our knowledge. Based on the available evidence, we consider this variant to be likely pathogenic; however, based on the presence of a homozygous individual in a control dataset, it may represent an allele which requires a stronger loss of function allele on the opposite chromosome for disease phenotypes to manifest. ACMG Criteria: PM3, PP3, PP4, PS4
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with tooth agenesis, selective, 10 (MIM#620173) and ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis (MIM#618180). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from aspartic acid to asparagine. (I) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (592 heterozygotes, 1 homozygote). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been classified as benign, likely benign, a VUS and pathogenic by clinical laboratories in ClinVar. The variant has also been observed as compound heterozygous or homozygous in eight families with hypodontia and ectodermal dysplasia in the literature, and was classified as a VUS or as likely pathogenic (PMID: 34042254, 27736875, 37009414). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Clinical, genetic, epidemiologic, evolutionary, and functional delineation of TSPEAR-related autosomal recessive ectodermal dysplasia 14. | Jackson A | HGG advances | 2023 | PMID: 37009414 |
| TSPEAR variants are primarily associated with ectodermal dysplasia and tooth agenesis but not hearing loss: A novel cohort study. | Bowles B | American journal of medical genetics. Part A | 2021 | PMID: 34042254 |
| Identification of likely pathogenic and known variants in TSPEAR, LAMB3, BCOR, and WNT10A in four Turkish families with tooth agenesis. | Du R | Human genetics | 2018 | PMID: 30046887 |
| Ashkenazi Jewish genomic variants: integrating data from the Israeli National Genetic Database and gnomAD. | Zlotogora J | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29144512 |
| Mutations in TSPEAR, Encoding a Regulator of Notch Signaling, Affect Tooth and Hair Follicle Morphogenesis. | Peled A | PLoS genetics | 2016 | PMID: 27736875 |
| Germline recessive mutations in PI4KA are associated with perisylvian polymicrogyria, cerebellar hypoplasia and arthrogryposis. | Pagnamenta AT | Human molecular genetics | 2015 | PMID: 25855803 |
Text-mined citations for rs138480801 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 30, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.