chr4-113088729-C-T

Position:

• chr4-113088729-C-T

Variant summary

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

The NM_001148.6(ANK2):​c.84+38917C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 151,934 control chromosomes in the GnomAD database, including 39,230 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 0.70 (39230 hom., cov: 31)
• Consequence: ANK2 NM_001148.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK2	NM_001148.6	c.84+38917C>T		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+38917C>T		intron_variant		1	NM_001148.6	ENSP00000349588.4

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106942 AN: 151816 Hom.: 39166 Cov.: 31

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.705 AC: 107061 AN: 151934 Hom.: 39230 Cov.: 31 AF XY: 0.703 AC XY: 52191 AN XY: 74238

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.684

Alfa AF: 0.626 Hom.: 39404

Bravo AF: 0.717

Asia WGS AF: 0.769 AC: 2673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.37

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: rs649022; hg19: chr4-114009885;