VCV000976480.1 - ClinVar

NM_002397.5(MEF2C):c.532C>T (p.Gln178Ter)

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.

Likely pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_002397.5(MEF2C):c.532C>T (p.Gln178Ter)

Variation ID: 976480 Accession: VCV000976480.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q14.3 5: 88751914 (GRCh38) [ NCBI UCSC ] 5: 88047731 (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 17, 2020	Aug 17, 2020	Jan 17, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NM_002397.5:c.532C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002388.2:p.Gln178Ter	nonsense
NM_001131005.2:c.526C>T	NP_001124477.1:p.Gln176Ter	nonsense
NM_001193347.1:c.586C>T	NP_001180276.1:p.Gln196Ter	nonsense
NM_001193348.1:c.388C>T	NP_001180277.1:p.Gln130Ter	nonsense
NM_001193349.3:c.388C>T	NP_001180278.1:p.Gln130Ter	nonsense
NM_001193350.2:c.532C>T	NP_001180279.1:p.Gln178Ter	nonsense
NM_001308002.3:c.532C>T	NP_001294931.1:p.Gln178Ter	nonsense
NM_001363581.2:c.532C>T	NP_001350510.1:p.Gln178Ter	nonsense
NM_001364329.2:c.532C>T	NP_001351258.1:p.Gln178Ter	nonsense
NM_001364330.2:c.532C>T	NP_001351259.1:p.Gln178Ter	nonsense
NM_001364331.2:c.532C>T	NP_001351260.1:p.Gln178Ter	nonsense
NM_001364332.2:c.388C>T	NP_001351261.1:p.Gln130Ter	nonsense
NM_001364333.2:c.532C>T	NP_001351262.1:p.Gln178Ter	nonsense
NM_001364334.2:c.532C>T	NP_001351263.1:p.Gln178Ter	nonsense
NM_001364335.2:c.532C>T	NP_001351264.1:p.Gln178Ter	nonsense
NM_001364336.2:c.532C>T	NP_001351265.1:p.Gln178Ter	nonsense
NM_001364337.2:c.532C>T	NP_001351266.1:p.Gln178Ter	nonsense
NM_001364338.2:c.586C>T	NP_001351267.1:p.Gln196Ter	nonsense
NM_001364339.2:c.532C>T	NP_001351268.1:p.Gln178Ter	nonsense
NM_001364340.2:c.532C>T	NP_001351269.1:p.Gln178Ter	nonsense
NM_001364341.2:c.532C>T	NP_001351270.1:p.Gln178Ter	nonsense
NM_001364342.2:c.532C>T	NP_001351271.1:p.Gln178Ter	nonsense
NM_001364343.2:c.526C>T	NP_001351272.1:p.Gln176Ter	nonsense
NM_001364344.2:c.388C>T	NP_001351273.1:p.Gln130Ter	nonsense
NM_001364345.2:c.532C>T	NP_001351274.1:p.Gln178Ter	nonsense
NM_001364346.2:c.532C>T	NP_001351275.1:p.Gln178Ter	nonsense
NM_001364347.2:c.532C>T	NP_001351276.1:p.Gln178Ter	nonsense
NM_001364348.2:c.532C>T	NP_001351277.1:p.Gln178Ter	nonsense
NM_001364349.2:c.532C>T	NP_001351278.1:p.Gln178Ter	nonsense
NM_001364350.2:c.532C>T	NP_001351279.1:p.Gln178Ter	nonsense
NM_001364352.2:c.526C>T	NP_001351281.1:p.Gln176Ter	nonsense
NM_001364353.2:c.154C>T	NP_001351282.1:p.Gln52Ter	nonsense
NM_001364354.2:c.388C>T	NP_001351283.1:p.Gln130Ter	nonsense
NM_001364355.2:c.388C>T	NP_001351284.1:p.Gln130Ter	nonsense
NM_001364356.2:c.154C>T	NP_001351285.1:p.Gln52Ter	nonsense
NM_001364357.2:c.106C>T	NP_001351286.1:p.Gln36Ter	nonsense
NC_000005.10:g.88751914G>A
NC_000005.9:g.88047731G>A
NG_023427.1:g.157192C>T

... more HGVS ... less HGVS

Protein change

Q130*, Q176*, Q178*, Q196*, Q36*, Q52*

Other names

Canonical SPDI

NC_000005.10:88751913:G:A

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

dbSNP: rs1772953161 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.
MEF2C		Sufficient evidence for dosage pathogenicity	Little evidence for dosage pathogenicity	GRCh38 GRCh37	463	574

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.
Intellectual disability, autosomal dominant 20	Likely pathogenic (1)	no assertion criteria provided	Jan 17, 2019	RCV001253802.2

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 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.
Likely pathogenic (Jan 17, 2019)	no assertion criteria provided Method: clinical testing	Intellectual disability, autosomal dominant 20 (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Clinical Genomics Laboratory, Stanford Medicine Accession: SCV001427026.1 First in ClinVar: Aug 17, 2020 Last updated: Aug 17, 2020	Comment: This variant is a predicted loss of function variant in the MEF2C gene. Loss of function variants in the MEF2C gene are an established cause … (more) This variant is a predicted loss of function variant in the MEF2C gene. Loss of function variants in the MEF2C gene are an established cause of disease. This variant has not been previously reported in association with disease. This variant was also absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, we conclude that there is sufficient evidence to classify the this variant as likely pathogenic for disease in an autosomal dominant manner. [ACMG evidence codes used: PVS1, PM2] (less)

Comment:

This variant is a predicted loss of function variant in the MEF2C gene. Loss of function variants in the MEF2C gene are an established cause of disease. This variant has not been previously reported in association with disease. This variant was also absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, we conclude that there is sufficient evidence to classify the this variant as likely pathogenic for disease in an autosomal dominant manner. [ACMG evidence codes used: PVS1, PM2]

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:

Citations for germline classification of this variant

There 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 rs1772953161 ...

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 Sep 17, 2024

ClinVar Genomic variation as it relates to human health

NM_002397.5(MEF2C):c.532C>T (p.Gln178Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1772953161 ...