VCV003075527.1 - ClinVar

NM_016203.4(PRKAG2):c.1386dup (p.Val463fs)

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.

Uncertain significance

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_016203.4(PRKAG2):c.1386dup (p.Val463fs)

Variation ID: 3075527 Accession: VCV003075527.1

Type and length

Duplication, 1 bp

Location

Cytogenetic: 7q36.1 7: 151565732-151565733 (GRCh38) [ NCBI UCSC ] 7: 151262818-151262819 (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 20, 2024	Apr 20, 2024	Jun 26, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_016203.4:c.1386dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_057287.2:p.Val463fs	frameshift
NM_001040633.2:c.1254dup	NP_001035723.1:p.Val419fs	frameshift
NM_001304527.2:c.1011dup	NP_001291456.1:p.Val338fs	frameshift
NM_001304531.2:c.663dup	NP_001291460.1:p.Val222fs	frameshift
NM_001363698.2:c.1014dup	NP_001350627.1:p.Val339fs	frameshift
NM_001407021.1:c.1386dup	NP_001393950.1:p.Val463fs	frameshift
NM_001407022.1:c.1383dup	NP_001393951.1:p.Val462fs	frameshift
NM_001407023.1:c.1383dup	NP_001393952.1:p.Val462fs	frameshift
NM_001407024.1:c.1254dup	NP_001393953.1:p.Val419fs	frameshift
NM_001407026.1:c.1251dup	NP_001393955.1:p.Val418fs	frameshift
NM_001407027.1:c.1251dup	NP_001393956.1:p.Val418fs	frameshift
NM_001407028.1:c.1014dup	NP_001393957.1:p.Val339fs	frameshift
NM_001407029.1:c.1011dup	NP_001393958.1:p.Val338fs	frameshift
NM_001407030.1:c.1098dup	NP_001393959.1:p.Val367fs	frameshift
NM_001407031.1:c.1095dup	NP_001393960.1:p.Val366fs	frameshift
NM_001407032.1:c.1068dup	NP_001393961.1:p.Val357fs	frameshift
NM_001407033.1:c.1062dup	NP_001393962.1:p.Val355fs	frameshift
NM_001407034.1:c.663dup	NP_001393963.1:p.Val222fs	frameshift
NM_001407035.1:c.663dup	NP_001393964.1:p.Val222fs	frameshift
NM_001407036.1:c.660dup	NP_001393965.1:p.Val221fs	frameshift
NM_001407037.1:c.723dup	NP_001393966.1:p.Val242fs	frameshift
NM_001407038.1:c.711dup	NP_001393967.1:p.Val238fs	frameshift
NM_001407039.1:c.660dup	NP_001393968.1:p.Val221fs	frameshift
NM_001407040.1:c.660dup	NP_001393969.1:p.Val221fs	frameshift
NM_024429.2:c.663dup	NP_077747.1:p.Val222fs	frameshift
NC_000007.14:g.151565734dup
NC_000007.13:g.151262820dup
NG_007486.2:g.316499dup
LRG_430:g.316499dup
LRG_430t1:c.1386dup	LRG_430p1:p.Val463fs

... more HGVS ... less HGVS

Protein change

V221fs, V222fs, V238fs, V242fs, V338fs, V339fs, V355fs, V357fs, V366fs, V367fs, V418fs, V419fs, V462fs, V463fs

Other names

Canonical SPDI

NC_000007.14:151565732:AA:AAA

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

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.
PRKAG2		No evidence available	No evidence available	GRCh38 GRCh37	1131	1308

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.
Hypertrophic cardiomyopathy	Uncertain significance (1)	criteria provided, single submitter	Jun 26, 2023	RCV004017045.2

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.
Uncertain Significance (Jun 26, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hypertrophic cardiomyopathy (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	All of Us Research Program, National Institutes of Health Accession: SCV004842215.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 Comment: This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more) This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)	Comment: This variant inserts 1 nucleotide in exon 12 of the PRKAG2 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more) This variant inserts 1 nucleotide in exon 12 of the PRKAG2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The role of loss-of-function PRKAG2 truncation and splice variants in autosomal dominant cardiovascular disorders is not clearly established. 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) Number of individuals with the variant: 1

Comment:

This variant inserts 1 nucleotide in exon 12 of the PRKAG2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The role of loss-of-function PRKAG2 truncation and splice variants in autosomal dominant cardiovascular disorders is not clearly established. 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.

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 this variant ...

Record last updated May 08, 2024

ClinVar Genomic variation as it relates to human health

NM_016203.4(PRKAG2):c.1386dup (p.Val463fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...