VCV001700577.1 - ClinVar

NM_032793.5(MFSD2A):c.750_753del (p.Cys251fs)

Germline

Classification

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.

(1)

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.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_032793.5(MFSD2A):c.750_753del (p.Cys251fs)

Variation ID: 1700577 Accession: VCV001700577.1

Type and length

Deletion, 4 bp

Location

Cytogenetic: 1p34.2 1: 39966633-39966636 (GRCh38) [ NCBI UCSC ] 1: 40432305-40432308 (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	Aug 15, 2022	Aug 15, 2022	Aug 11, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_032793.5:c.750_753del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_116182.2:p.Cys251fs	frameshift
NM_001136493.3:c.789_792del	NP_001129965.1:p.Cys264fs	frameshift
NM_001287808.2:c.282_285del	NP_001274737.1:p.Cys95fs	frameshift
NM_001287809.2:c.633_636del	NP_001274738.1:p.Cys212fs	frameshift
NM_001349821.2:c.744_747del	NP_001336750.1:p.Cys249fs	frameshift
NM_001349822.2:c.750_753del	NP_001336751.1:p.Cys251fs	frameshift
NM_001349823.2:c.405_408del	NP_001336752.1:p.Cys136fs	frameshift
NR_109896.2:n.898_901del		non-coding transcript variant
NC_000001.11:g.39966636_39966639del
NC_000001.10:g.40432308_40432311del
NG_053084.1:g.16525_16528del

... more HGVS ... less HGVS

Protein change

C136fs, C212fs, C249fs, C251fs, C264fs, C95fs

Other names

Canonical SPDI

NC_000001.11:39966632:TGTCTGT:TGT

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

OMIM: 614397.0006 dbSNP: rs1278119822 VarSome

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
Gene	OMIM	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.
MFSD2A		-	-	GRCh38 GRCh37	163	175

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.
Microcephaly 15, primary, autosomal recessive	Pathogenic (1)	no assertion criteria provided	Aug 11, 2022	RCV002274821.1

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.
Pathogenic (Aug 11, 2022)	no assertion criteria provided Method: literature only	NEURODEVELOPMENTAL DISORDER WITH PROGRESSIVE MICROCEPHALY, SPASTICITY, AND BRAIN IMAGING ABNORMALITIES Affected status: not provided Allele origin: germline	OMIM Accession: SCV002559814.1 First in ClinVar: Aug 15, 2022 Last updated: Aug 15, 2022	Publications: PubMed (1) PubMed: 32572202 Comment on evidence: By whole-exome sequencing in a 4-month-old Saudi girl (patient 8), born to consanguineous parents, with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities … (more) By whole-exome sequencing in a 4-month-old Saudi girl (patient 8), born to consanguineous parents, with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities (NEDMISBA; 616486), Scala et al. (2020) identified a homozygous 4-bp deletion (c.750_753del, NM_032793.5) in the MFSD2A gene, which resulted in a frameshift and a premature stop codon (Cys251SerfsTer3). The mutation segregated with the disorder in the family and was not present in homozygosity in public variant databases, including gnomAD. (less)

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

Title	Author	Journal	Year	Link
Biallelic MFSD2A variants associated with congenital microcephaly, developmental delay, and recognizable neuroimaging features.	Scala M	European journal of human genetics : EJHG	2020	PMID: 32572202

Text-mined citations for rs1278119822 ...

These 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 Dec 25, 2023

ClinVar Genomic variation as it relates to human health

NM_032793.5(MFSD2A):c.750_753del (p.Cys251fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1278119822 ...