2-75493270-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135032.2(EVA1A):c.425T>C(p.Val142Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EVA1A NM_001135032.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.09

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13008386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVA1A	NM_001135032.2	c.425T>C	p.Val142Ala	missense_variant	4/4	ENST00000393913.8
EVA1A	NM_001369524.1	c.425T>C	p.Val142Ala	missense_variant	6/6
EVA1A	NM_001369525.1	c.425T>C	p.Val142Ala	missense_variant	5/5
EVA1A	NM_032181.3	c.425T>C	p.Val142Ala	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVA1A	ENST00000393913.8	c.425T>C	p.Val142Ala	missense_variant	4/4	1	NM_001135032.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461398 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726976

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.425T>C (p.V142A) alteration is located in exon 4 (coding exon 2) of the EVA1A gene. This alteration results from a T to C substitution at nucleotide position 425, causing the valine (V) at amino acid position 142 to be replaced by an alanine (A). 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	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	18
Dann	Benign	0.93
DEOGEN2	Benign	0.0064	T;T;T;T;T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.61
FATHMM_MKL	Uncertain	0.77	D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.096	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.61	N;N;N;.;N;.
MutationTaster	Benign	0.93	N;N;N;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N
REVEL	Benign	0.095
Sift	Benign	0.30	T;T;T;T;T;D
Sift4G	Benign	0.18	T;T;T;T;T;.
Polyphen		0.0010	B;B;B;.;B;.
Vest4		0.10
MutPred		0.19		Gain of disorder (P = 0.0432);Gain of disorder (P = 0.0432);Gain of disorder (P = 0.0432);.;Gain of disorder (P = 0.0432);Gain of disorder (P = 0.0432);
MVP		0.35
MPC		0.45
ClinPred		0.18	T
GERP RS		-0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.026
gMVP		0.41

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: chr2-75720396;