rs6533660

chr4-112939764-A-Gchr4-112939764-A-T

Variant summary

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

The ENST00000506722.5(ANK2):c.21+35250A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,100 control chromosomes in the GnomAD database, including 18,639 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 0.44 (18639 hom., cov: 32)
• Consequence: ANK2 ENST00000506722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK2	NM_001127493.3	c.21+35250A>G		intron_variant
ANK2	NM_001354239.2	c.21+35250A>G		intron_variant
ANK2	NM_001354243.2	c.21+35250A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK2	ENST00000506722.5	c.21+35250A>G		intron_variant		1
ANK2	ENST00000503271.5	c.21+35250A>G		intron_variant		2
ANK2	ENST00000503423.6	c.21+35250A>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66199 AN: 151982 Hom.: 18586 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.436 AC: 66311 AN: 152100 Hom.: 18639 Cov.: 32 AF XY: 0.434 AC XY: 32265 AN XY: 74356

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.430

Alfa AF: 0.337 Hom.: 2528

Bravo AF: 0.465

Asia WGS AF: 0.618 AC: 2145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.28
Dann	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6533660; hg19: chr4-113860920;