rs6533660

Variant names:

• chr4-112939764-A-G
• rs6533660
• ENST00000506722.5:c.21+35250A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-112939764-A-G
• chr4-112939764-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ANK2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, ClinGen
• Brugada syndrome

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, ClinGen
• catecholaminergic polymorphic ventricular tachycardia

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp
• heart conduction disease

  Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• cardiac arrhythmia, ankyrin-B-related

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• long QT syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ANK2	NM_001386142.1	c.21+35250A>G		intron_variant	Intron 2 of 44		NP_001373071.1
ANK2	NM_001386143.1	c.21+35250A>G		intron_variant	Intron 2 of 47		NP_001373072.1
ANK2	NM_001386186.2	c.72+233547A>G		intron_variant	Intron 1 of 46		NP_001373115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK2	ENST00000506722.5	c.21+35250A>G		intron_variant	Intron 2 of 46	1		ENSP00000421067.1
ANK2	ENST00000672209.1	c.21+35250A>G		intron_variant	Intron 2 of 47			ENSP00000499982.1
ANK2	ENST00000673298.1	c.21+35250A>G		intron_variant	Intron 2 of 46			ENSP00000500245.1

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

African (AFR) AF: 0.781 AC: 32413 AN: 41494

American (AMR) AF: 0.359 AC: 5486 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1056 AN: 3468

East Asian (EAS) AF: 0.706 AC: 3646 AN: 5164

South Asian (SAS) AF: 0.481 AC: 2309 AN: 4804

European-Finnish (FIN) AF: 0.199 AC: 2104 AN: 10592

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17919 AN: 67990

Other (OTH) AF: 0.430 AC: 908 AN: 2110

Alfa AF: 0.346 Hom.: 4545

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
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6533660; hg19: chr4-113860920;