2-189689757-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001378068.1(ANKAR):​c.832G>T​(p.Asp278Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,350 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ANKAR
NM_001378068.1 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.82
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANKARNM_001378068.1 linkuse as main transcriptc.832G>T p.Asp278Tyr missense_variant 3/23 ENST00000684021.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKARENST00000684021.1 linkuse as main transcriptc.832G>T p.Asp278Tyr missense_variant 3/23 NM_001378068.1 P1Q7Z5J8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460350
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726544
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsJul 13, 2022The c.832G>T (p.D278Y) alteration is located in exon 3 (coding exon 2) of the ANKAR gene. This alteration results from a G to T substitution at nucleotide position 832, causing the aspartic acid (D) at amino acid position 278 to be replaced by a tyrosine (Y). 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
0.32
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.070
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.060
T;T
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.81
.;T
M_CAP
Benign
0.014
T
MetaRNN
Uncertain
0.65
D;D
MetaSVM
Benign
-0.53
T
MutationAssessor
Uncertain
2.2
M;M
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-3.4
D;D
REVEL
Uncertain
0.35
Sift
Uncertain
0.0010
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;D
Vest4
0.58
MutPred
0.40
Gain of ubiquitination at K274 (P = 0.0773);Gain of ubiquitination at K274 (P = 0.0773);
MVP
0.85
MPC
0.55
ClinPred
0.98
D
GERP RS
6.0
Varity_R
0.59
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-190554483; API