VCV000538815.7 - ClinVar

NM_002397.5(MEF2C):c.1247C>T (p.Ala416Val)

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.

(2)

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.

Uncertain significance

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_002397.5(MEF2C):c.1247C>T (p.Ala416Val)

Variation ID: 538815 Accession: VCV000538815.7

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q14.3 5: 88722779 (GRCh38) [ NCBI UCSC ] 5: 88018596 (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	May 28, 2018	Feb 14, 2024	Jul 19, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_002397.5:c.1247C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002388.2:p.Ala416Val	missense
NM_001131005.2:c.1217C>T	NP_001124477.1:p.Ala406Val	missense
NM_001193347.1:c.1277C>T	NP_001180276.1:p.Ala426Val	missense
NM_001193348.1:c.1079C>T	NP_001180277.1:p.Ala360Val	missense
NM_001193349.3:c.1007C>T	NP_001180278.1:p.Ala336Val	missense
NM_001193350.2:c.1247C>T	NP_001180279.1:p.Ala416Val	missense
NM_001308002.3:c.1223C>T	NP_001294931.1:p.Ala408Val	missense
NM_001363581.2:c.1151C>T	NP_001350510.1:p.Ala384Val	missense
NM_001364329.2:c.1247C>T	NP_001351258.1:p.Ala416Val	missense
NM_001364330.2:c.1247C>T	NP_001351259.1:p.Ala416Val	missense
NM_001364331.2:c.1247C>T	NP_001351260.1:p.Ala416Val	missense
NM_001364332.2:c.1007C>T	NP_001351261.1:p.Ala336Val	missense
NM_001364333.2:c.1223C>T	NP_001351262.1:p.Ala408Val	missense
NM_001364334.2:c.1151C>T	NP_001351263.1:p.Ala384Val	missense
NM_001364335.2:c.1151C>T	NP_001351264.1:p.Ala384Val	missense
NM_001364336.2:c.1151C>T	NP_001351265.1:p.Ala384Val	missense
NM_001364337.2:c.1151C>T	NP_001351266.1:p.Ala384Val	missense
NM_001364338.2:c.1181C>T	NP_001351267.1:p.Ala394Val	missense
NM_001364339.2:c.1127C>T	NP_001351268.1:p.Ala376Val	missense
NM_001364340.2:c.1127C>T	NP_001351269.1:p.Ala376Val	missense
NM_001364341.2:c.1127C>T	NP_001351270.1:p.Ala376Val	missense
NM_001364342.2:c.1127C>T	NP_001351271.1:p.Ala376Val	missense
NM_001364343.2:c.1121C>T	NP_001351272.1:p.Ala374Val	missense
NM_001364344.2:c.1103C>T	NP_001351273.1:p.Ala368Val	missense
NM_001364345.2:c.1149C>T	NP_001351274.1:p.Gly383=	synonymous
NM_001364346.2:c.1149C>T	NP_001351275.1:p.Gly383=	synonymous
NM_001364347.2:c.1149C>T	NP_001351276.1:p.Gly383=	synonymous
NM_001364348.2:c.1125C>T	NP_001351277.1:p.Gly375=	synonymous
NM_001364349.2:c.1125C>T	NP_001351278.1:p.Gly375=	synonymous
NM_001364350.2:c.1125C>T	NP_001351279.1:p.Gly375=	synonymous
NM_001364352.2:c.1119C>T	NP_001351281.1:p.Gly373=	synonymous
NM_001364353.2:c.869C>T	NP_001351282.1:p.Ala290Val	missense
NM_001364354.2:c.1005C>T	NP_001351283.1:p.Gly335=	synonymous
NM_001364355.2:c.1005C>T	NP_001351284.1:p.Gly335=	synonymous
NM_001364356.2:c.773C>T	NP_001351285.1:p.Ala258Val	missense
NM_001364357.2:c.701C>T	NP_001351286.1:p.Ala234Val	missense
NR_146284.1:n.411G>A		non-coding transcript variant
NC_000005.10:g.88722779G>A
NC_000005.9:g.88018596G>A
NG_023427.1:g.186327C>T

... more HGVS ... less HGVS

Protein change

A406V, A416V, A384V, A426V, A408V, A234V, A258V, A336V, A360V, A376V, A394V, A290V, A368V, A374V

Other names

Canonical SPDI

NC_000005.10:88722778: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.

Exome Aggregation Consortium (ExAC) 0.00001

Links

ClinGen: CA3337185 dbSNP: rs768570497 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	465	576
MEF2C-AS2	-	-	-	GRCh38	-	84

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	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Jul 19, 2022	RCV000648311.7

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.
Uncertain significance (Nov 22, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Intellectual disability, autosomal dominant 20 Affected status: yes Allele origin: germline	Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV001429039.1 First in ClinVar: Aug 15, 2020 Last updated: Aug 15, 2020	Number of individuals with the variant: 1
Uncertain significance (Jul 19, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Intellectual disability, autosomal dominant 20 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000770125.5 First in ClinVar: May 28, 2018 Last updated: Feb 14, 2024	Comment: In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more) In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 538815). This variant has not been reported in the literature in individuals affected with MEF2C-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 416 of the MEF2C protein (p.Ala416Val). (less)

Comment:

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 538815). This variant has not been reported in the literature in individuals affected with MEF2C-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 416 of the MEF2C protein (p.Ala416Val).

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 rs768570497 ...

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 29, 2024

ClinVar Genomic variation as it relates to human health

NM_002397.5(MEF2C):c.1247C>T (p.Ala416Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs768570497 ...