8-86012784-T-C

Variant names:

• chr8-86012784-T-C
• rs285406
• ENST00000521564.1:c.-263+25384T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521564.1(ATP6V0D2):​c.-263+25384T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 152,268 control chromosomes in the GnomAD database, including 68,439 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 0.95 (68439 hom., cov: 32)
• Consequence: ATP6V0D2 ENST00000521564.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

Genes affected

ATP6V0D2 (HGNC:18266): (ATPase H+ transporting V0 subunit d2) Predicted to enable proton transmembrane transporter activity. Predicted to be involved in vacuolar acidification and vacuolar transport. Located in apical plasma membrane. Part of vacuolar proton-transporting V-type ATPase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0D2	ENST00000521564.1	c.-263+25384T>C		intron_variant	Intron 1 of 3	3		ENSP00000429731.1

Frequencies

GnomAD3 genomes AF: 0.947 AC: 144157 AN: 152150 Hom.: 68379 Cov.: 32

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.943

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.948 AC: 144275 AN: 152268 Hom.: 68439 Cov.: 32 AF XY: 0.947 AC XY: 70502 AN XY: 74450

Gnomad4 AFR AF: 0.986

Gnomad4 AMR AF: 0.950

Gnomad4 ASJ AF: 0.939

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.970

Gnomad4 FIN AF: 0.937

Gnomad4 NFE AF: 0.920

Gnomad4 OTH AF: 0.943

Alfa AF: 0.925 Hom.: 85493

Bravo AF: 0.951

Asia WGS AF: 0.987 AC: 3428 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.7
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs285406; hg19: chr8-87025013;