ClinVar Genomic variation as it relates to human health
NM_024675.4(PALB2):c.3529G>A (p.Asp1177Asn)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_024675.4(PALB2):c.3529G>A (p.Asp1177Asn)
Variation ID: 2773991 Accession: VCV002773991.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p12.2 16: 23603491 (GRCh38) [ NCBI UCSC ] 16: 23614812 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Feb 14, 2024 May 1, 2024 Sep 16, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_024675.4:c.3529G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_078951.2:p.Asp1177Asn missense NM_001407296.1:c.3469G>A NP_001394225.1:p.Asp1157Asn missense NM_001407297.1:c.3457G>A NP_001394226.1:p.Asp1153Asn missense NM_001407298.1:c.3367G>A NP_001394227.1:p.Asp1123Asn missense NM_001407299.1:c.3292G>A NP_001394228.1:p.Asp1098Asn missense NM_001407300.1:c.3250G>A NP_001394229.1:p.Asp1084Asn missense NM_001407301.1:c.*164G>A 3 prime UTR NM_001407302.1:c.*164G>A 3 prime UTR NM_001407304.1:c.2644G>A NP_001394233.1:p.Asp882Asn missense NM_001407305.1:c.2644G>A NP_001394234.1:p.Asp882Asn missense NM_001407306.1:c.2644G>A NP_001394235.1:p.Asp882Asn missense NM_001407307.1:c.2482G>A NP_001394236.1:p.Asp828Asn missense NM_001407308.1:c.2407G>A NP_001394237.1:p.Asp803Asn missense NM_001407309.1:c.2407G>A NP_001394238.1:p.Asp803Asn missense NM_001407310.1:c.*164G>A 3 prime UTR NM_001407311.1:c.*164G>A 3 prime UTR NM_001407312.1:c.1741G>A NP_001394241.1:p.Asp581Asn missense NM_001407313.1:c.*164G>A 3 prime UTR NM_001407314.1:c.1063G>A NP_001394243.1:p.Asp355Asn missense NC_000016.10:g.23603491C>T NC_000016.9:g.23614812C>T NG_007406.1:g.42867G>A LRG_308:g.42867G>A LRG_308t1:c.3529G>A LRG_308p1:p.Asp1177Asn - Protein change
- D1084N, D1098N, D1123N, D1153N, D882N, D355N, D1157N, D581N, D803N, D1177N, D828N
- Other names
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- Canonical SPDI
- NC_000016.10:23603490:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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PALB2 | - | - |
GRCh38 GRCh37 |
5899 | 5940 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Sep 16, 2023 | RCV003585677.2 |
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
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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
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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
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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. |
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Uncertain significance
(Nov 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV004357056.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces aspartic acid with asparagine at codon 1177 of the PALB2 protein. Computational prediction suggests that this variant may not impact protein … (more)
This missense variant replaces aspartic acid with asparagine at codon 1177 of the PALB2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PALB2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Sep 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV005029019.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The p.D1177N variant (also known as c.3529G>A), located in coding exon 13 of the PALB2 gene, results from a G to A substitution at nucleotide … (more)
The p.D1177N variant (also known as c.3529G>A), located in coding exon 13 of the PALB2 gene, results from a G to A substitution at nucleotide position 3529. The aspartic acid at codon 1177 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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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. |
Citations for germline classification of this variant
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated May 08, 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.