NM_001135032.2:c.202G>T

Variant names:

• chr2-75493493-C-A
• rs1392515801
• NM_001135032.2:c.202G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135032.2(EVA1A):​c.202G>T​(p.Gly68Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G68R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EVA1A NM_001135032.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14967373).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135032.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVA1A	NM_001135032.2	MANE Select	c.202G>T	p.Gly68Trp	missense	Exon 4 of 4	NP_001128504.1	Q9H8M9
	EVA1A	NM_001369524.1		c.202G>T	p.Gly68Trp	missense	Exon 6 of 6	NP_001356453.1	Q9H8M9
	EVA1A	NM_001369525.1		c.202G>T	p.Gly68Trp	missense	Exon 5 of 5	NP_001356454.1	Q9H8M9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVA1A	ENST00000393913.8	TSL:1 MANE Select	c.202G>T	p.Gly68Trp	missense	Exon 4 of 4	ENSP00000377490.3	Q9H8M9
	EVA1A	ENST00000910300.1		c.259G>T	p.Gly87Trp	missense	Exon 4 of 4	ENSP00000580359.1
	EVA1A	ENST00000910305.1		c.259G>T	p.Gly87Trp	missense	Exon 3 of 3	ENSP00000580364.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.6
DANN	Benign	0.93
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.72
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.10
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.016	D
Polyphen		0.95	P
Vest4		0.18
MutPred		0.26		Loss of disorder (P = 0.0174)
MVP		0.27
MPC		0.77
ClinPred		0.63	D
GERP RS		-5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.18
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1392515801; hg19: chr2-75720619; COSMIC: COSV52061909; COSMIC: COSV52061909;