rs2272231

Positions:

chr4-113339336-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001148.6(ANK2):c.3893+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,600,286 control chromosomes in the GnomAD database, including 17,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 5205 hom., cov: 32)

Exomes 𝑓: 0.11 ( 11826 hom. )

Consequence

ANK2
NM_001148.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.695

Variant links:

Genes affected

ANK2 (HGNC:493): (ankyrin 2) This gene encodes a member of the ankyrin family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton. Ankyrins play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. The protein encoded by this gene is required for targeting and stability of Na/Ca exchanger 1 in cardiomyocytes. Mutations in this gene cause long QT syndrome 4 and cardiac arrhythmia syndrome. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2011]

ANK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 4-113339336-G-T is Benign according to our data. Variant chr4-113339336-G-T is described in ClinVar as [Benign]. Clinvar id is 136391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113339336-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK2	NM_001148.6 linkuse as main transcript	c.3893+14G>T		intron_variant		ENST00000357077.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK2	ENST00000357077.9 linkuse as main transcript	c.3893+14G>T		intron_variant		1	NM_001148.6	A2	Q01484-4

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30931

AN:

152000

Hom.:

5181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.463

Gnomad AMI

AF:

0.0341

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.0971

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0626

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.131

AC:

32906

AN:

251208

Hom.:

3305

AF XY:

0.124

AC XY:

16876

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.475

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.0987

Gnomad EAS exome

AF:

0.120

Gnomad SAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.0616

Gnomad NFE exome

AF:

0.0999

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.112

AC:

161934

AN:

1448168

Hom.:

11826

Cov.:

AF XY:

0.112

AC XY:

80443

AN XY:

721434

show subpopulations

Gnomad4 AFR exome

AF:

0.477

Gnomad4 AMR exome

AF:

0.138

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.125

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.0660

Gnomad4 NFE exome

AF:

0.0993

Gnomad4 OTH exome

AF:

0.130

GnomAD4 genome

AF:

0.204

AC:

30999

AN:

152118

Hom.:

5205

Cov.:

AF XY:

0.199

AC XY:

14769

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.464

Gnomad4 AMR

AF:

0.148

Gnomad4 ASJ

AF:

0.0971

Gnomad4 EAS

AF:

0.117

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.0626

Gnomad4 NFE

AF:

0.101

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.172

Hom.:

868

Bravo

AF:

0.222

Asia WGS

AF:

0.142

AC:

492

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2012	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Cardiac arrhythmia, ankyrin-B-related

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Long QT syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.0

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over