4-113032425-C-T

Position:

• chr4-113032425-C-T

Variant summary

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

The NM_001386142.1(ANK2):​c.21+127911C>T 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 151,876 control chromosomes in the GnomAD database, including 3,404 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 (3404 hom., cov: 32)
• Consequence: ANK2 NM_001386142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK2	NM_001386142.1	c.21+127911C>T		intron_variant			NP_001373071.1
ANK2	NM_001386143.1	c.21+127911C>T		intron_variant			NP_001373072.1
ANK2	NM_001386186.2	c.73-141991C>T		intron_variant			NP_001373115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK2	ENST00000506722.5	c.21+127911C>T		intron_variant		1		ENSP00000421067.1
ANK2	ENST00000672209.1	c.21+127911C>T		intron_variant				ENSP00000499982.1
ANK2	ENST00000673298.1	c.21+127911C>T		intron_variant				ENSP00000500245.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29636 AN: 151758 Hom.: 3393 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.195 AC: 29649 AN: 151876 Hom.: 3404 Cov.: 32 AF XY: 0.204 AC XY: 15122 AN XY: 74238

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.186

Alfa AF: 0.193 Hom.: 4207

Bravo AF: 0.193

Asia WGS AF: 0.294 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1395114; hg19: chr4-113953581;