rs10516593

chr4-113157656-A-Cchr4-113157656-A-T

Variant summary

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

The NM_001148.6(ANK2):c.85-16760A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,122 control chromosomes in the GnomAD database, including 36,290 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 0.69 (36290 hom., cov: 32)
• Consequence: ANK2 NM_001148.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914

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 (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK2	NM_001148.6	c.85-16760A>C		intron_variant		ENST00000357077.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK2	ENST00000357077.9	c.85-16760A>C		intron_variant		1	NM_001148.6	A2

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104133 AN: 152004 Hom.: 36227 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.685 AC: 104254 AN: 152122 Hom.: 36290 Cov.: 32 AF XY: 0.685 AC XY: 50946 AN XY: 74370

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.646

Alfa AF: 0.629 Hom.: 35616

Bravo AF: 0.687

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.2
Dann	Benign	0.71

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: rs10516593; hg19: chr4-114078812;