rs13134375

Positions:

• chr4-113157775-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000357077.9(ANK2):​c.85-16641T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,140 control chromosomes in the GnomAD database, including 7,445 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 0.30 (7445 hom., cov: 32)
• Consequence: ANK2 ENST00000357077.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK2	NM_001148.6	c.85-16641T>C		intron_variant		ENST00000357077.9	NP_001139.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK2	ENST00000357077.9	c.85-16641T>C		intron_variant		1	NM_001148.6	ENSP00000349588	A2

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45312 AN: 152022 Hom.: 7443 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.0400

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.298 AC: 45325 AN: 152140 Hom.: 7445 Cov.: 32 AF XY: 0.289 AC XY: 21515 AN XY: 74370

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.0401

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.306

Alfa AF: 0.366 Hom.: 9030

Bravo AF: 0.288

Asia WGS AF: 0.150 AC: 525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.0
DANN	Benign	0.21

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

Other links and lift over

dbSNP: rs13134375; hg19: chr4-114078931;