2-46512073-C-T

Variant names:

• chr2-46512073-C-T
• rs139290779
• NM_001318063.2:c.639G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001318063.2(ATP6V1E2):​c.639G>A​(p.Met213Ile) 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. 16/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M213T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP6V1E2 NM_001318063.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 0 publications found

Genes affected

ATP6V1E2 (HGNC:18125): (ATPase H+ transporting V1 subunit E2) Predicted to enable P-type proton-exporting transporter activity. Predicted to act upstream of or within proton transmembrane transport. Predicted to be located in cytosol. Predicted to be part of proton-transporting two-sector ATPase complex, catalytic domain. [provided by Alliance of Genome Resources, Apr 2022]

LINC02583 (HGNC:53812): (long intergenic non-protein coding RNA 2583)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05121571).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318063.2. 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
	ATP6V1E2	NM_001318063.2	MANE Select	c.639G>A	p.Met213Ile	missense	Exon 5 of 5	NP_001304992.1	A0A140VKA8
	ATP6V1E2	NM_001371281.1		c.639G>A	p.Met213Ile	missense	Exon 5 of 5	NP_001358210.1	Q96A05
	ATP6V1E2	NM_001371282.1		c.639G>A	p.Met213Ile	missense	Exon 5 of 5	NP_001358211.1	A0A140VKA8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1E2	ENST00000522587.6	TSL:3 MANE Select	c.639G>A	p.Met213Ile	missense	Exon 5 of 5	ENSP00000428141.1	Q96A05
	ATP6V1E2	ENST00000306448.4	TSL:1	c.639G>A	p.Met213Ile	missense	Exon 2 of 2	ENSP00000304891.4	Q96A05
	ATP6V1E2	ENST00000890126.1		c.639G>A	p.Met213Ile	missense	Exon 6 of 6	ENSP00000560185.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.2
DANN	Benign	0.90
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.074	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.048
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.0060
Sift	Benign	0.16	T
Sift4G	Benign	0.19	T
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.43		Loss of catalytic residue at M213 (P = 0.0589)
MVP		0.076
MPC		0.015
ClinPred		0.21	T
GERP RS		2.4
Varity_R		0.095
gMVP		0.28
Mutation Taster		=95/5	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: rs139290779; hg19: chr2-46739212;