4-112861770-T-C

Position:

• chr4-112861770-T-C

Variant summary

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

The ENST00000506722.5(ANK2):​c.-39-42685T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,644 control chromosomes in the GnomAD database, including 22,709 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 0.53 (22709 hom., cov: 30)
• Consequence: ANK2 ENST00000506722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK2	NM_001127493.3	c.-39-42685T>C		intron_variant
ANK2	NM_001354239.2	c.-39-42685T>C		intron_variant
ANK2	NM_001354243.2	c.-39-42685T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK2	ENST00000506722.5	c.-39-42685T>C		intron_variant		1
ANK2	ENST00000503271.5	c.-39-42685T>C		intron_variant		2
ANK2	ENST00000503423.6	c.-39-42685T>C		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.534 AC: 80885 AN: 151526 Hom.: 22647 Cov.: 30

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.534 AC: 81011 AN: 151644 Hom.: 22709 Cov.: 30 AF XY: 0.539 AC XY: 39965 AN XY: 74092

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.512

Alfa AF: 0.454 Hom.: 21037

Bravo AF: 0.551

Asia WGS AF: 0.690 AC: 2395 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs895763; hg19: chr4-113782926;