rs10090327

Variant names:

• chr8-86033676-A-C
• rs10090327
• ENST00000521564.1:c.-262-32712A>C

Variant summary

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

The ENST00000521564.1(ATP6V0D2):​c.-262-32712A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,186 control chromosomes in the GnomAD database, including 4,733 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 0.24 (4733 hom., cov: 32)
• Consequence: ATP6V0D2 ENST00000521564.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 6 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 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.-262-32712A>C		intron	N/A	ENSP00000429731.1	E5RHJ7

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35774 AN: 152068 Hom.: 4736 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.235 AC: 35774 AN: 152186 Hom.: 4733 Cov.: 32 AF XY: 0.234 AC XY: 17439 AN XY: 74396

African (AFR) AF: 0.115 AC: 4760 AN: 41538

American (AMR) AF: 0.268 AC: 4099 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1187 AN: 3468

East Asian (EAS) AF: 0.410 AC: 2117 AN: 5164

South Asian (SAS) AF: 0.309 AC: 1491 AN: 4826

European-Finnish (FIN) AF: 0.222 AC: 2351 AN: 10590

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18824 AN: 67996

Other (OTH) AF: 0.258 AC: 545 AN: 2112

Alfa AF: 0.265 Hom.: 6573

Bravo AF: 0.231

Asia WGS AF: 0.329 AC: 1147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.52
PhyloP100		1.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10090327;

hg19: chr8-87045905;