rs139268603

Variant names:

• chr2-46512452-C-A
• NM_001318063.2:c.260G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-46512452-C-A
• chr2-46512452-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001318063.2(ATP6V1E2):​c.260G>T​(p.Arg87Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,892 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. R87Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ATP6V1E2 NM_001318063.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.932

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V1E2	NM_001318063.2	c.260G>T	p.Arg87Leu	missense_variant	Exon 5 of 5	ENST00000522587.6	NP_001304992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1E2	ENST00000522587.6	c.260G>T	p.Arg87Leu	missense_variant	Exon 5 of 5	3	NM_001318063.2	ENSP00000428141.1
ATP6V1E2	ENST00000306448.4	c.260G>T	p.Arg87Leu	missense_variant	Exon 2 of 2	1		ENSP00000304891.4
ATP6V1E2	ENST00000524249.5	n.776-21621G>T		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T
Eigen	Benign	0.091
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Pathogenic	4.0	H;H
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-6.4	D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;D
Vest4		0.70
MutPred		0.74		Loss of MoRF binding (P = 0.0452);Loss of MoRF binding (P = 0.0452);
MVP		0.21
MPC		0.11
ClinPred		1.0	D
GERP RS		0.52
Varity_R		0.90
gMVP		0.71

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: chr2-46739591;