chr2-189689917-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001378068.1(ANKAR):ā€‹c.992A>Gā€‹(p.Lys331Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000115 in 1,396,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.000011 ( 0 hom. )

Consequence

ANKAR
NM_001378068.1 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21
Variant links:
Genes affected
ANKAR (HGNC:26350): (ankyrin and armadillo repeat containing) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04613787).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANKARNM_001378068.1 linkuse as main transcriptc.992A>G p.Lys331Arg missense_variant 3/23 ENST00000684021.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKARENST00000684021.1 linkuse as main transcriptc.992A>G p.Lys331Arg missense_variant 3/23 NM_001378068.1 P1Q7Z5J8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000155
AC:
3
AN:
193682
Hom.:
0
AF XY:
0.00000945
AC XY:
1
AN XY:
105796
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:
0.0000313
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000115
AC:
16
AN:
1396760
Hom.:
0
Cov.:
30
AF XY:
0.00000722
AC XY:
5
AN XY:
692426
show subpopulations
Gnomad4 AFR exome
AF:
0.0000329
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:
0.0000138
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000826
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 27, 2023The c.992A>G (p.K331R) alteration is located in exon 3 (coding exon 2) of the ANKAR gene. This alteration results from a A to G substitution at nucleotide position 992, causing the lysine (K) at amino acid position 331 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0040
T;T
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.66
.;T
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.046
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.97
L;L
MutationTaster
Benign
0.94
N;N;N;N;N
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.53
N;N
REVEL
Benign
0.015
Sift
Benign
0.42
T;T
Sift4G
Benign
0.81
T;T
Polyphen
0.0070
B;B
Vest4
0.082
MutPred
0.21
Loss of methylation at K331 (P = 0.0401);Loss of methylation at K331 (P = 0.0401);
MVP
0.55
MPC
0.081
ClinPred
0.091
T
GERP RS
0.84
Varity_R
0.032
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs773295578; hg19: chr2-190554643; API