chr8-86012784-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ATP6V0D2 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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 (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000521564.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0D2	ENST00000521564.1	TSL:3	c.-263+25384T>C		intron	N/A	ENSP00000429731.1	E5RHJ7

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

African (AFR) AF: 0.986 AC: 40992 AN: 41582

American (AMR) AF: 0.950 AC: 14518 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 3259 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5183 AN: 5184

South Asian (SAS) AF: 0.970 AC: 4680 AN: 4826

European-Finnish (FIN) AF: 0.937 AC: 9939 AN: 10606

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.920 AC: 62589 AN: 67998

Other (OTH) AF: 0.943 AC: 1996 AN: 2116

Alfa AF: 0.932 Hom.: 150241

Bravo AF: 0.951

Asia WGS AF: 0.987 AC: 3428 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.7
DANN	Benign	0.83
PhyloP100		-0.066

Splicing

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

Other links and lift over

dbSNP: rs285406; hg19: chr8-87025013;