rs375502760

Variant names:

• chr2-75493415-C-G
• NM_001135032.2:c.280G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-75493415-C-G
• chr2-75493415-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001135032.2(EVA1A):​c.280G>C​(p.Asp94His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. D94N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EVA1A NM_001135032.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.16

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVA1A	NM_001135032.2	c.280G>C	p.Asp94His	missense_variant	Exon 4 of 4	ENST00000393913.8	NP_001128504.1
EVA1A	NM_001369524.1	c.280G>C	p.Asp94His	missense_variant	Exon 6 of 6		NP_001356453.1
EVA1A	NM_001369525.1	c.280G>C	p.Asp94His	missense_variant	Exon 5 of 5		NP_001356454.1
EVA1A	NM_032181.3	c.280G>C	p.Asp94His	missense_variant	Exon 4 of 4		NP_115557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVA1A	ENST00000393913.8	c.280G>C	p.Asp94His	missense_variant	Exon 4 of 4	1	NM_001135032.2	ENSP00000377490.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727244

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T;T;T;T;T;T;.
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	.;D;.;D;.;D;D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.77	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.8	M;M;M;.;M;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.9	D;D;D;D;D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.014	D;D;D;D;D;D;D
Sift4G	Uncertain	0.011	D;D;D;D;D;.;D
Polyphen		1.0	D;D;D;.;D;.;.
Vest4		0.58
MutPred		0.25		Loss of loop (P = 0.0389);Loss of loop (P = 0.0389);Loss of loop (P = 0.0389);.;Loss of loop (P = 0.0389);Loss of loop (P = 0.0389);Loss of loop (P = 0.0389);
MVP		0.76
MPC		1.3
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.41
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-75720541;