rs12503758

Positions:

• chr4-112927886-T-A
• chr4-112927886-T-G

Variant summary

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

The ENST00000506722.5(ANK2):​c.21+23372T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,108 control chromosomes in the GnomAD database, including 16,691 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 0.39 (16691 hom., cov: 32)
• Consequence: ANK2 ENST00000506722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK2	NM_001127493.3	c.21+23372T>A		intron_variant
ANK2	NM_001354239.2	c.21+23372T>A		intron_variant
ANK2	NM_001354243.2	c.21+23372T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK2	ENST00000506722.5	c.21+23372T>A		intron_variant		1
ANK2	ENST00000503271.5	c.21+23372T>A		intron_variant		2
ANK2	ENST00000503423.6	c.21+23372T>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59666 AN: 151990 Hom.: 16628 Cov.: 32

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.393 AC: 59795 AN: 152108 Hom.: 16691 Cov.: 32 AF XY: 0.391 AC XY: 29058 AN XY: 74344

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.394

Alfa AF: 0.287 Hom.: 1338

Bravo AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12503758; hg19: chr4-113849042;