2-75493493-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001135032.2(EVA1A):​c.202G>A​(p.Gly68Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

EVA1A
NM_001135032.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.716
Variant links:
Genes affected
EVA1A (HGNC:25816): (eva-1 homolog A, regulator of programmed cell death) Predicted to be involved in apoptotic process and autophagy. Located in intracellular membrane-bounded organelle and plasma 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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.021823108).
BP6
Variant 2-75493493-C-T is Benign according to our data. Variant chr2-75493493-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3276640.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EVA1ANM_001135032.2 linkc.202G>A p.Gly68Arg missense_variant Exon 4 of 4 ENST00000393913.8 NP_001128504.1 Q9H8M9
EVA1ANM_001369524.1 linkc.202G>A p.Gly68Arg missense_variant Exon 6 of 6 NP_001356453.1
EVA1ANM_001369525.1 linkc.202G>A p.Gly68Arg missense_variant Exon 5 of 5 NP_001356454.1
EVA1ANM_032181.3 linkc.202G>A p.Gly68Arg missense_variant Exon 4 of 4 NP_115557.1 Q9H8M9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EVA1AENST00000393913.8 linkc.202G>A p.Gly68Arg missense_variant Exon 4 of 4 1 NM_001135032.2 ENSP00000377490.3 Q9H8M9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461868
Hom.:
0
Cov.:
30
AF XY:
0.0000110
AC XY:
8
AN XY:
727232
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:
0.0000162
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
May 08, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.056
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
0.29
DANN
Benign
0.59
DEOGEN2
Benign
0.0033
T;T;T;T;T;T;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.023
N
LIST_S2
Benign
0.53
.;T;.;T;.;T;T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.022
T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.86
N;N;N;.;N;.;.
PrimateAI
Benign
0.23
T
PROVEAN
Benign
0.91
N;N;N;N;N;N;N
REVEL
Benign
0.039
Sift
Benign
0.57
T;T;T;T;T;T;T
Sift4G
Benign
0.60
T;T;T;T;T;.;T
Polyphen
0.0010
B;B;B;.;B;.;.
Vest4
0.083
MutPred
0.23
Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);.;Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);
MVP
0.18
MPC
0.44
ClinPred
0.018
T
GERP RS
-5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.019
gMVP
0.14

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: rs1392515801; hg19: chr2-75720619; API