chr4-113012812-A-T

Position:

• chr4-113012812-A-T

Variant summary

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

The ENST00000506722.5(ANK2):​c.21+108298A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,950 control chromosomes in the GnomAD database, including 25,539 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 0.56 (25539 hom., cov: 32)
• Consequence: ANK2 ENST00000506722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222

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:40076): (ANK2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK2	NM_001127493.3	c.21+108298A>T		intron_variant
ANK2	NM_001354239.2	c.21+108298A>T		intron_variant
ANK2	NM_001354243.2	c.21+108298A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK2-AS1	ENST00000508959.1	n.237+21871T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84841 AN: 151832 Hom.: 25549 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.558 AC: 84834 AN: 151950 Hom.: 25539 Cov.: 32 AF XY: 0.554 AC XY: 41175 AN XY: 74272

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.582

Alfa AF: 0.619 Hom.: 3761

Bravo AF: 0.555

Asia WGS AF: 0.464 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs961294; hg19: chr4-113933968;