rs29307

Variant summary

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

The NM_001148.6(ANK2):​c.2475+1512G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 152,172 control chromosomes in the GnomAD database, including 287 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 0.042 ( 287 hom., cov: 32)

Consequence

ANK2
NM_001148.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.556
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANK2NM_001148.6 linkuse as main transcriptc.2475+1512G>C intron_variant ENST00000357077.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANK2ENST00000357077.9 linkuse as main transcriptc.2475+1512G>C intron_variant 1 NM_001148.6 A2Q01484-4

Frequencies

GnomAD3 genomes
AF:
0.0423
AC:
6436
AN:
152056
Hom.:
288
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0286
Gnomad AMI
AF:
0.0680
Gnomad AMR
AF:
0.0299
Gnomad ASJ
AF:
0.00750
Gnomad EAS
AF:
0.264
Gnomad SAS
AF:
0.0255
Gnomad FIN
AF:
0.0435
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.0392
Gnomad OTH
AF:
0.0406
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0423
AC:
6434
AN:
152172
Hom.:
287
Cov.:
32
AF XY:
0.0429
AC XY:
3189
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.0285
Gnomad4 AMR
AF:
0.0300
Gnomad4 ASJ
AF:
0.00750
Gnomad4 EAS
AF:
0.264
Gnomad4 SAS
AF:
0.0253
Gnomad4 FIN
AF:
0.0435
Gnomad4 NFE
AF:
0.0392
Gnomad4 OTH
AF:
0.0402
Alfa
AF:
0.0418
Hom.:
22
Bravo
AF:
0.0430
Asia WGS
AF:
0.0980
AC:
340
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.91
DANN
Benign
0.39

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

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

Other links and lift over

dbSNP: rs29307; hg19: chr4-114216206; API