rs1351998

Positions:

• chr4-113147771-G-C
• chr4-113147771-G-T

Variant summary

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

The NM_001148.6(ANK2):​c.85-26645G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,052 control chromosomes in the GnomAD database, including 17,568 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 0.47 (17568 hom., cov: 33)
• Consequence: ANK2 NM_001148.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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 (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK2	NM_001148.6	c.85-26645G>C		intron_variant		ENST00000357077.9	NP_001139.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK2	ENST00000357077.9	c.85-26645G>C		intron_variant		1	NM_001148.6	ENSP00000349588	A2

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71151 AN: 151934 Hom.: 17524 Cov.: 33

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.469 AC: 71258 AN: 152052 Hom.: 17568 Cov.: 33 AF XY: 0.470 AC XY: 34915 AN XY: 74316

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.452

Alfa AF: 0.428 Hom.: 1802

Bravo AF: 0.488

Asia WGS AF: 0.399 AC: 1389 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.58
DANN	Benign	0.41

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: rs1351998; hg19: chr4-114068927;