rs2026893

Variant names:

• chr13-41822482-G-T
• rs2026893
• NM_015058.2:c.1701-3096C>A

Variant summary

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

The NM_015058.2(VWA8):​c.1701-3096C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 152,168 control chromosomes in the GnomAD database, including 170 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 0.044 (170 hom., cov: 32)
• Consequence: VWA8 NM_015058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 1 publications found

Genes affected

VWA8 (HGNC:29071): (von Willebrand factor A domain containing 8) Predicted to enable ATP binding activity. Located in mitochondrion and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

VWA8 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 97

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA8	NM_015058.2	c.1701-3096C>A		intron_variant	Intron 14 of 44	ENST00000379310.8	NP_055873.1
VWA8	NM_001009814.2	c.1701-3096C>A		intron_variant	Intron 14 of 25		NP_001009814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA8	ENST00000379310.8	c.1701-3096C>A		intron_variant	Intron 14 of 44	2	NM_015058.2	ENSP00000368612.3
VWA8	ENST00000281496.6	c.1701-3096C>A		intron_variant	Intron 14 of 25	1		ENSP00000281496.6

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6624 AN: 152050 Hom.: 165 Cov.: 32

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0489

Gnomad ASJ AF: 0.0912

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0395

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0436 AC: 6630 AN: 152168 Hom.: 170 Cov.: 32 AF XY: 0.0434 AC XY: 3231 AN XY: 74406

African (AFR) AF: 0.0376 AC: 1561 AN: 41520

American (AMR) AF: 0.0493 AC: 753 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0912 AC: 316 AN: 3466

East Asian (EAS) AF: 0.117 AC: 604 AN: 5180

South Asian (SAS) AF: 0.0446 AC: 215 AN: 4826

European-Finnish (FIN) AF: 0.0335 AC: 355 AN: 10594

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0395 AC: 2684 AN: 67996

Other (OTH) AF: 0.0431 AC: 91 AN: 2112

Alfa AF: 0.0392 Hom.: 16

Bravo AF: 0.0444

Asia WGS AF: 0.0780 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.83
DANN	Benign	0.35
PhyloP100		-0.047
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: rs2026893; hg19: chr13-42396618;