rs12503758

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000506722.5(ANK2):​c.21+23372T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,108 control chromosomes in the GnomAD database, including 16,691 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 0.39 ( 16691 hom., cov: 32)

Consequence

ANK2
ENST00000506722.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.163
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANK2NM_001127493.3 linkuse as main transcriptc.21+23372T>A intron_variant
ANK2NM_001354239.2 linkuse as main transcriptc.21+23372T>A intron_variant
ANK2NM_001354243.2 linkuse as main transcriptc.21+23372T>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANK2ENST00000506722.5 linkuse as main transcriptc.21+23372T>A intron_variant 1 Q01484-5
ANK2ENST00000503271.5 linkuse as main transcriptc.21+23372T>A intron_variant 2
ANK2ENST00000503423.6 linkuse as main transcriptc.21+23372T>A intron_variant 5 A2

Frequencies

GnomAD3 genomes
AF:
0.393
AC:
59666
AN:
151990
Hom.:
16628
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.785
Gnomad AMI
AF:
0.281
Gnomad AMR
AF:
0.329
Gnomad ASJ
AF:
0.252
Gnomad EAS
AF:
0.475
Gnomad SAS
AF:
0.399
Gnomad FIN
AF:
0.156
Gnomad MID
AF:
0.351
Gnomad NFE
AF:
0.207
Gnomad OTH
AF:
0.389
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.393
AC:
59795
AN:
152108
Hom.:
16691
Cov.:
32
AF XY:
0.391
AC XY:
29058
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.785
Gnomad4 AMR
AF:
0.329
Gnomad4 ASJ
AF:
0.252
Gnomad4 EAS
AF:
0.475
Gnomad4 SAS
AF:
0.399
Gnomad4 FIN
AF:
0.156
Gnomad4 NFE
AF:
0.207
Gnomad4 OTH
AF:
0.394
Alfa
AF:
0.287
Hom.:
1338
Bravo
AF:
0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
1.2
DANN
Benign
0.45

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12503758; hg19: chr4-113849042; API