2-75493511-C-T

Variant names:

• chr2-75493511-C-T
• rs150035696
• NM_001135032.2:c.184G>A

Variant summary

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

The NM_001135032.2(EVA1A):​c.184G>A​(p.Asp62Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000691 in 1,614,232 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00076 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (0 hom.)
• Consequence: EVA1A NM_001135032.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.71
• Publications: 2 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.

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.184G>A	p.Asp62Asn	missense	Exon 4 of 4	NP_001128504.1	Q9H8M9
	EVA1A	NM_001369524.1		c.184G>A	p.Asp62Asn	missense	Exon 6 of 6	NP_001356453.1	Q9H8M9
	EVA1A	NM_001369525.1		c.184G>A	p.Asp62Asn	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.184G>A	p.Asp62Asn	missense	Exon 4 of 4	ENSP00000377490.3	Q9H8M9
	EVA1A	ENST00000910300.1		c.241G>A	p.Asp81Asn	missense	Exon 4 of 4	ENSP00000580359.1
	EVA1A	ENST00000910305.1		c.241G>A	p.Asp81Asn	missense	Exon 3 of 3	ENSP00000580364.1

Frequencies

GnomAD3 genomes AF: 0.000762 AC: 116 AN: 152240 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000629 AC: 158 AN: 251268 AF XY: 0.000685

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000555

Gnomad NFE exome AF: 0.00121

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000684 AC: 1000 AN: 1461874 Hom.: 0 Cov.: 30 AF XY: 0.000688 AC XY: 500 AN XY: 727238

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.000487 AC: 26 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000837 AC: 931 AN: 1112010

Other (OTH) AF: 0.000580 AC: 35 AN: 60396

GnomAD4 genome AF: 0.000761 AC: 116 AN: 152358 Hom.: 1 Cov.: 33 AF XY: 0.000698 AC XY: 52 AN XY: 74502

African (AFR) AF: 0.0000240 AC: 1 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00162 AC: 110 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00113 Hom.: 1

Bravo AF: 0.000529

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00186 AC: 16

ExAC AF: 0.000626 AC: 76

EpiCase AF: 0.00115

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.32
Sift	Benign	0.049	D
Sift4G	Benign	0.20	T
Polyphen		1.0	D
Vest4		0.78
MVP		0.81
MPC		1.1
ClinPred		0.26	T
GERP RS		4.9
Varity_R		0.33
gMVP		0.60
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.28		Position offset: -8

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

Other links and lift over

dbSNP: rs150035696; hg19: chr2-75720637;