4-113092484-T-G

Position:

• chr4-113092484-T-G

Variant summary

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

The NM_001148.6(ANK2):​c.84+42672T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 150,200 control chromosomes in the GnomAD database, including 3,737 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 0.20 (3737 hom., cov: 33)
• Consequence: ANK2 NM_001148.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK2	NM_001148.6	c.84+42672T>G		intron_variant		ENST00000357077.9	NP_001139.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK2	ENST00000357077.9	c.84+42672T>G		intron_variant		1	NM_001148.6	ENSP00000349588	A2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29345 AN: 150088 Hom.: 3737 Cov.: 33

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0714

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.195 AC: 29346 AN: 150200 Hom.: 3737 Cov.: 33 AF XY: 0.190 AC XY: 13942 AN XY: 73334

Gnomad4 AFR AF: 0.0524

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.0712

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.183

Alfa AF: 0.243 Hom.: 1223

Bravo AF: 0.176

Asia WGS AF: 0.0900 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.58

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: rs11726138; hg19: chr4-114013640;