2-46519824-A-G

Variant names:

• chr2-46519824-A-G
• rs4952830
• ENST00000306448.4:c.-981T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000306448.4(ATP6V1E2):​c.-981T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,026 control chromosomes in the GnomAD database, including 8,006 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (8006 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ATP6V1E2 ENST00000306448.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000306448.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1E2	NM_001318063.2	MANE Select	c.-101-7012T>C		intron	N/A	NP_001304992.1
	ATP6V1E2	NM_001371281.1		c.-101-7012T>C		intron	N/A	NP_001358210.1
	ATP6V1E2	NM_001371282.1		c.-101-7012T>C		intron	N/A	NP_001358211.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1E2	ENST00000306448.4	TSL:1	c.-981T>C		5_prime_UTR	Exon 1 of 2	ENSP00000304891.4
	ATP6V1E2	ENST00000522587.6	TSL:3 MANE Select	c.-101-7012T>C		intron	N/A	ENSP00000428141.1
	ATP6V1E2	ENST00000524249.5	TSL:5	n.775+15989T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47734 AN: 151906 Hom.: 7999 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.0621

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.314 AC: 47753 AN: 152022 Hom.: 8006 Cov.: 32 AF XY: 0.310 AC XY: 23031 AN XY: 74320

African (AFR) AF: 0.242 AC: 10033 AN: 41444

American (AMR) AF: 0.356 AC: 5437 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1346 AN: 3472

East Asian (EAS) AF: 0.0621 AC: 321 AN: 5172

South Asian (SAS) AF: 0.187 AC: 898 AN: 4810

European-Finnish (FIN) AF: 0.316 AC: 3337 AN: 10574

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25352 AN: 67952

Other (OTH) AF: 0.324 AC: 684 AN: 2114

Alfa AF: 0.334 Hom.: 17455

Bravo AF: 0.314

Asia WGS AF: 0.162 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.67
PhyloP100		-1.1
PromoterAI		0.031	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs4952830; hg19: chr2-46746963;