4-113353931-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_001148.6(ANK2):​c.5313G>T​(p.Lys1771Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K1771K) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ANK2
NM_001148.6 missense

Scores

2
12
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.85
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 Likely_benign. Variant got -3 ACMG points.

PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ANK2. . Gene score misZ 1.9641 (greater than the threshold 3.09). Trascript score misZ 4.2513 (greater than threshold 3.09). GenCC has associacion of gene with heart conduction disease, Brugada syndrome, long QT syndrome, complex neurodevelopmental disorder, cardiac arrhythmia, ankyrin-B-related, catecholaminergic polymorphic ventricular tachycardia.
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ANK2NM_001148.6 linkuse as main transcriptc.5313G>T p.Lys1771Asn missense_variant 38/46 ENST00000357077.9 NP_001139.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANK2ENST00000357077.9 linkuse as main transcriptc.5313G>T p.Lys1771Asn missense_variant 38/461 NM_001148.6 ENSP00000349588 A2Q01484-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250866
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135572
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461820
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Benign
0.0086
T
BayesDel_noAF
Benign
-0.23
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T;T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Uncertain
0.20
D
MetaRNN
Uncertain
0.56
D;D
MetaSVM
Uncertain
-0.074
T
MutationAssessor
Uncertain
2.3
M;.
MutationTaster
Benign
0.68
D;D;D;D;D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.9
N;N
REVEL
Uncertain
0.39
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.035
D;D
Vest4
0.49
MVP
0.75
MPC
0.46
ClinPred
0.92
D
GERP RS
4.0
Varity_R
0.46
gMVP
0.11

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: rs140992864; hg19: chr4-114275087; API