VCV000222501.19 - ClinVar

NM_001148.6(ANK2):c.7247G>A (p.Arg2416Gln)

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.

(5)

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_001148.6(ANK2):c.7247G>A (p.Arg2416Gln)

Variation ID: 222501 Accession: VCV000222501.19

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 4q26 4: 113355865 (GRCh38) [ NCBI UCSC ] 4: 114277021 (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	Mar 1, 2016	Oct 20, 2024	May 11, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001148.6:c.7247G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001139.3:p.Arg2416Gln	missense
NM_001127493.3:c.4400-4958G>A		intron variant
NM_001354225.2:c.4439-4958G>A		intron variant
NM_001354228.2:c.4328-4958G>A		intron variant
NM_001354230.2:c.4406-4958G>A		intron variant
NM_001354231.2:c.4469-4958G>A		intron variant
NM_001354232.2:c.4463-4958G>A		intron variant
NM_001354235.2:c.4424-4958G>A		intron variant
NM_001354236.2:c.4325-4958G>A		intron variant
NM_001354237.2:c.4505-4958G>A		intron variant
NM_001354239.2:c.4397-4958G>A		intron variant
NM_001354240.2:c.4472-4958G>A		intron variant
NM_001354241.2:c.4472-4958G>A		intron variant
NM_001354242.2:c.4469-4958G>A		intron variant
NM_001354243.2:c.4364-4958G>A		intron variant
NM_001354244.2:c.4361-4958G>A		intron variant
NM_001354245.2:c.4265-4958G>A		intron variant
NM_001354246.2:c.4424-4958G>A		intron variant
NM_001354249.2:c.4241-4958G>A		intron variant
NM_001354252.2:c.4397-4958G>A		intron variant
NM_001354253.2:c.4202-4958G>A		intron variant
NM_001354254.2:c.4376-4958G>A		intron variant
NM_001354255.2:c.4364-4958G>A		intron variant
NM_001354256.2:c.4361-4958G>A		intron variant
NM_001354257.2:c.4166-4958G>A		intron variant
NM_001354258.2:c.4328-4958G>A		intron variant
NM_001354260.2:c.4142-4958G>A		intron variant
NM_001354261.2:c.4286-4958G>A		intron variant
NM_001354262.2:c.4265-4958G>A		intron variant
NM_001354264.2:c.4262-4958G>A		intron variant
NM_001354265.2:c.4424-4958G>A		intron variant
NM_001354266.2:c.4241-4958G>A		intron variant
NM_001354267.2:c.4241-4958G>A		intron variant
NM_001354268.2:c.4229-4958G>A		intron variant
NM_001354269.3:c.4214-4958G>A		intron variant
NM_001354270.2:c.4202-4958G>A		intron variant
NM_001354271.2:c.4142-4958G>A		intron variant
NM_001354272.2:c.4298-4958G>A		intron variant
NM_001354273.2:c.4127-4958G>A		intron variant
NM_001354274.2:c.4193-4958G>A		intron variant
NM_001354275.2:c.4265-4958G>A		intron variant
NM_001354276.2:c.4241-4958G>A		intron variant
NM_001354277.2:c.4043-4958G>A		intron variant
NM_001354278.2:c.1955-4958G>A		intron variant
NM_001354279.2:c.1991-4958G>A		intron variant
NM_001354280.2:c.1976-4958G>A		intron variant
NM_001354281.2:c.1955-4958G>A		intron variant
NM_001354282.2:c.1991-4958G>A		intron variant
NM_001386142.1:c.7013G>A	NP_001373071.1:p.Arg2338Gln	missense
NM_001386143.1:c.4364-4958G>A		intron variant
NM_001386144.1:c.4472-4958G>A		intron variant
NM_001386146.1:c.4208-4958G>A		intron variant
NM_001386147.1:c.4253-4958G>A		intron variant
NM_001386148.2:c.4412-4958G>A		intron variant
NM_001386149.1:c.4208-4958G>A		intron variant
NM_001386150.1:c.4208-4958G>A		intron variant
NM_001386151.1:c.4142-4958G>A		intron variant
NM_001386152.1:c.4484-4958G>A		intron variant
NM_001386153.1:c.4208-4958G>A		intron variant
NM_001386154.1:c.4193-4958G>A		intron variant
NM_001386156.1:c.4166-4958G>A		intron variant
NM_001386157.1:c.4043-4958G>A		intron variant
NM_001386158.1:c.3944-4958G>A		intron variant
NM_001386160.1:c.4271-4958G>A		intron variant
NM_001386161.1:c.4361-4958G>A		intron variant
NM_001386162.1:c.4241-4958G>A		intron variant
NM_001386166.1:c.3647G>A	NP_001373095.1:p.Arg1216Gln	missense
NM_001386167.1:c.827-4958G>A		intron variant
NM_001386174.1:c.7388G>A	NP_001373103.1:p.Arg2463Gln	missense
NM_001386175.1:c.7364G>A	NP_001373104.1:p.Arg2455Gln	missense
NM_001386186.2:c.4412-4958G>A		intron variant
NM_001386187.2:c.4292-4958G>A		intron variant
NM_020977.5:c.4427-4958G>A		intron variant
NC_000004.12:g.113355865G>A
NC_000004.11:g.114277021G>A
NG_009006.2:g.542783G>A
LRG_327:g.542783G>A
LRG_327t1:c.7247G>A

... more HGVS ... less HGVS

Protein change

R2416Q, R1216Q, R2338Q, R2455Q, R2463Q

Other names

Canonical SPDI

NC_000004.12:113355864: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.

The Genome Aggregation Database (gnomAD) 0.00001

Exome Aggregation Consortium (ExAC) 0.00002

The Genome Aggregation Database (gnomAD), exomes 0.00002

Trans-Omics for Precision Medicine (TOPMed) 0.00002

Links

ClinGen: CA353922 dbSNP: rs766001488 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.
ANK2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2676	3263
LOC126807137	-	-	-	GRCh38	-	292

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.
Arrhythmogenic right ventricular cardiomyopathy	Uncertain significance (1)	criteria provided, single submitter	Apr 14, 2015	RCV000208158.1
Long QT syndrome	Uncertain significance (1)	criteria provided, single submitter	Dec 31, 2022	RCV001853294.6
not provided	Uncertain significance (1)	criteria provided, single submitter	Sep 1, 2023	RCV003430769.10
not specified	Uncertain significance (1)	criteria provided, single submitter	Nov 14, 2023	RCV003479060.1
Cardiovascular phenotype	Uncertain significance (1)	criteria provided, single submitter	May 11, 2024	RCV004639177.1

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.
Uncertain significance (Nov 14, 2023)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV004223798.1 First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024
Uncertain significance (Dec 31, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Long QT syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002198330.3 First in ClinVar: Mar 28, 2022 Last updated: Feb 20, 2024	Comment: This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2416 of the ANK2 protein (p.Arg2416Gln). … (more) This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2416 of the ANK2 protein (p.Arg2416Gln). 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 222501). This variant has not been reported in the literature in individuals affected with ANK2-related conditions. This variant is present in population databases (rs766001488, gnomAD 0.007%). (less)
Uncertain significance (Apr 14, 2015)	criteria provided, single submitter (Variant Classification) Method: clinical testing	Arrhythmogenic right ventricular cardiomyopathy Affected status: yes Allele origin: germline	Blueprint Genetics Accession: SCV000263777.2 First in ClinVar: Mar 01, 2016 Last updated: Mar 01, 2016	Number of individuals with the variant: 1
Uncertain significance (May 11, 2024)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV005134133.1 First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024	Comment: The p.R2416Q variant (also known as c.7247G>A), located in coding exon 38 of the ANK2 gene, results from a G to A substitution at nucleotide … (more) The p.R2416Q variant (also known as c.7247G>A), located in coding exon 38 of the ANK2 gene, results from a G to A substitution at nucleotide position 7247. The arginine at codon 2416 is replaced by glutamine, 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. Based on the available evidence, the clinical significance of this variant remains unclear. (less)
Uncertain significance (Sep 01, 2023)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV004148747.10 First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024	Comment: ANK2: PM5, BP4 Number of individuals with the variant: 1

Comment:

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2416 of the ANK2 protein (p.Arg2416Gln). 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 222501). This variant has not been reported in the literature in individuals affected with ANK2-related conditions. This variant is present in population databases (rs766001488, gnomAD 0.007%).

Comment:

The p.R2416Q variant (also known as c.7247G>A), located in coding exon 38 of the ANK2 gene, results from a G to A substitution at nucleotide position 7247. The arginine at codon 2416 is replaced by glutamine, 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. Based on the available evidence, the clinical significance of this variant remains unclear.

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 rs766001488 ...

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 Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_001148.6(ANK2):c.7247G>A (p.Arg2416Gln)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs766001488 ...