chr4-113304675-T-G

Position:

• chr4-113304675-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.2548+1836T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,124 control chromosomes in the GnomAD database, including 47,567 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 0.79 (47567 hom., cov: 33)
• Consequence: ANK2 NM_001148.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK2	NM_001148.6	c.2548+1836T>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.2548+1836T>G		intron_variant		1	NM_001148.6	ENSP00000349588.4

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119825 AN: 152006 Hom.: 47505 Cov.: 33

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.788 AC: 119945 AN: 152124 Hom.: 47567 Cov.: 33 AF XY: 0.791 AC XY: 58824 AN XY: 74362

Gnomad4 AFR AF: 0.863

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.749

Gnomad4 OTH AF: 0.742

Alfa AF: 0.762 Hom.: 26001

Bravo AF: 0.788

Asia WGS AF: 0.759 AC: 2620 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.9
DANN	Benign	0.75

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: rs29311; hg19: chr4-114225831;