ENST00000506722.5:c.21+120714T>C

Variant names:

• chr4-113025228-T-C
• rs1395112
• ENST00000506722.5:c.21+120714T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000506722.5(ANK2):​c.21+120714T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,048 control chromosomes in the GnomAD database, including 29,796 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 0.62 (29796 hom., cov: 32)
• Consequence: ANK2 ENST00000506722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 2 publications found

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]

LOC124900761 (HGNC:):

ANK2-AS1 (HGNC:40076): (ANK2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124900761	XR_007058234.1	n.3705T>C		non_coding_transcript_exon_variant	Exon 1 of 2
ANK2	NM_001386142.1	c.21+120714T>C		intron_variant	Intron 2 of 44		NP_001373071.1
ANK2	NM_001386143.1	c.21+120714T>C		intron_variant	Intron 2 of 47		NP_001373072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK2	ENST00000506722.5	c.21+120714T>C		intron_variant	Intron 2 of 46	1		ENSP00000421067.1
ANK2	ENST00000672209.1	c.21+120714T>C		intron_variant	Intron 2 of 47			ENSP00000499982.1
ANK2	ENST00000673298.1	c.21+120714T>C		intron_variant	Intron 2 of 46			ENSP00000500245.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94378 AN: 151930 Hom.: 29778 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.621 AC: 94434 AN: 152048 Hom.: 29796 Cov.: 32 AF XY: 0.623 AC XY: 46328 AN XY: 74308

African (AFR) AF: 0.507 AC: 21005 AN: 41466

American (AMR) AF: 0.674 AC: 10291 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2214 AN: 3470

East Asian (EAS) AF: 0.589 AC: 3046 AN: 5172

South Asian (SAS) AF: 0.745 AC: 3593 AN: 4820

European-Finnish (FIN) AF: 0.643 AC: 6783 AN: 10554

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.668 AC: 45416 AN: 67978

Other (OTH) AF: 0.640 AC: 1355 AN: 2116

Alfa AF: 0.648 Hom.: 72691

Bravo AF: 0.621

Asia WGS AF: 0.656 AC: 2280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.40
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1395112; hg19: chr4-113946384;