rs632895

Variant names:

• chr4-113067357-G-A
• rs632895
• NM_001148.6:c.84+17545G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001148.6(ANK2):​c.84+17545G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,028 control chromosomes in the GnomAD database, including 5,777 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (5777 hom., cov: 32)
• Consequence: ANK2 NM_001148.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.594
• Publications: 2 publications found

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-AS1 (HGNC:40076): (ANK2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK2	NM_001148.6	c.84+17545G>A		intron_variant	Intron 1 of 45	ENST00000357077.9	NP_001139.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK2	ENST00000357077.9	c.84+17545G>A		intron_variant	Intron 1 of 45	1	NM_001148.6	ENSP00000349588.4

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35481 AN: 151910 Hom.: 5768 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0503

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0728

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.242

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.234 AC: 35540 AN: 152028 Hom.: 5777 Cov.: 32 AF XY: 0.229 AC XY: 16988 AN XY: 74322

African (AFR) AF: 0.462 AC: 19121 AN: 41398

American (AMR) AF: 0.228 AC: 3480 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 588 AN: 3470

East Asian (EAS) AF: 0.0501 AC: 259 AN: 5172

South Asian (SAS) AF: 0.165 AC: 794 AN: 4810

European-Finnish (FIN) AF: 0.0728 AC: 773 AN: 10612

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9696 AN: 67990

Other (OTH) AF: 0.243 AC: 514 AN: 2116

Alfa AF: 0.169 Hom.: 5180

Bravo AF: 0.254

Asia WGS AF: 0.139 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.44
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs632895; hg19: chr4-113988513;