4-113295768-C-T

Position:

• chr4-113295768-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.2475+2230C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,992 control chromosomes in the GnomAD database, including 18,060 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 0.48 (18060 hom., cov: 32)
• Consequence: ANK2 NM_001148.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK2	NM_001148.6	c.2475+2230C>T		intron_variant		ENST00000357077.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK2	ENST00000357077.9	c.2475+2230C>T		intron_variant		1	NM_001148.6	A2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73382 AN: 151874 Hom.: 18043 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.483 AC: 73434 AN: 151992 Hom.: 18060 Cov.: 32 AF XY: 0.478 AC XY: 35536 AN XY: 74282

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.472

Alfa AF: 0.498 Hom.: 31531

Bravo AF: 0.474

Asia WGS AF: 0.356 AC: 1238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.89
DANN	Benign	0.45

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: rs29305; hg19: chr4-114216924;