rs362468

Positions:

• chr4-113225218-C-T

Variant summary

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

The NM_001148.6(ANK2):​c.385-6943C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 152,212 control chromosomes in the GnomAD database, including 85 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 0.012 (85 hom., cov: 32)
• Consequence: ANK2 NM_001148.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK2	NM_001148.6	c.385-6943C>T		intron_variant		ENST00000357077.9	NP_001139.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK2	ENST00000357077.9	c.385-6943C>T		intron_variant		1	NM_001148.6	ENSP00000349588	A2

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1863 AN: 152094 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0320

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.0248

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.0144

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

GnomAD4 genome AF: 0.0123 AC: 1878 AN: 152212 Hom.: 85 Cov.: 32 AF XY: 0.0133 AC XY: 993 AN XY: 74426

Gnomad4 AFR AF: 0.00233

Gnomad4 AMR AF: 0.0323

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.0251

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.00157

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0127 Hom.: 15

Bravo AF: 0.0155

Asia WGS AF: 0.115 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.26
DANN	Benign	0.43

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: rs362468; hg19: chr4-114146374;