4-113012812-A-T

Variant names:

• chr4-113012812-A-T
• rs961294
• ENST00000506722.5:c.21+108298A>T

Variant summary

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

The ENST00000506722.5(ANK2):​c.21+108298A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,950 control chromosomes in the GnomAD database, including 25,539 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 0.56 (25539 hom., cov: 32)
• Consequence: ANK2 ENST00000506722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK2	NM_001386142.1	c.21+108298A>T		intron_variant	Intron 2 of 44		NP_001373071.1
ANK2	NM_001386143.1	c.21+108298A>T		intron_variant	Intron 2 of 47		NP_001373072.1
ANK2	NM_001386186.2	c.73-161604A>T		intron_variant	Intron 1 of 46		NP_001373115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK2	ENST00000506722.5	c.21+108298A>T		intron_variant	Intron 2 of 46	1		ENSP00000421067.1
ANK2	ENST00000672209.1	c.21+108298A>T		intron_variant	Intron 2 of 47			ENSP00000499982.1
ANK2	ENST00000673298.1	c.21+108298A>T		intron_variant	Intron 2 of 46			ENSP00000500245.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84841 AN: 151832 Hom.: 25549 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.558 AC: 84834 AN: 151950 Hom.: 25539 Cov.: 32 AF XY: 0.554 AC XY: 41175 AN XY: 74272

African (AFR) AF: 0.317 AC: 13131 AN: 41462

American (AMR) AF: 0.628 AC: 9594 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2270 AN: 3470

East Asian (EAS) AF: 0.474 AC: 2452 AN: 5168

South Asian (SAS) AF: 0.543 AC: 2617 AN: 4816

European-Finnish (FIN) AF: 0.578 AC: 6087 AN: 10538

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46704 AN: 67912

Other (OTH) AF: 0.582 AC: 1226 AN: 2108

Alfa AF: 0.619 Hom.: 3761

Bravo AF: 0.555

Asia WGS AF: 0.464 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.53
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs961294; hg19: chr4-113933968;