rs9665610

Variant names:

• chr10-114248705-T-A
• rs9665610
• NM_001272046.2:c.-9T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-114248705-T-A
• chr10-114248705-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001272046.2(VWA2):​c.-9T>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,608,136 control chromosomes in the GnomAD database, including 4,920 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.093 (748 hom., cov: 32)
  • Exomes 𝑓: 0.073 (4172 hom.)
• Consequence: VWA2 NM_001272046.2 splice_region
• Scores: Splicing: ADA: 0.0005670
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0140
• Publications: 9 publications found

Genes affected

VWA2 (HGNC:24709): (von Willebrand factor A domain containing 2) This gene encodes a member of the von Willebrand factor A-like domain protein superfamily. The encoded protein is localized to the extracellular matrix and may serve as a structural component in basement membranes or in anchoring structures on scaffolds of collagen VII or fibrillin. This gene has been linked to type 1A diabetes and is a candidate serological marker for colon cancer. [provided by RefSeq, Jan 2013]

VWA2 Gene-Disease associations (from GenCC):

• congenital anomaly of kidney and urinary tract

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-114248705-T-A is Benign according to our data. Variant chr10-114248705-T-A is described in ClinVar as [Benign]. Clinvar id is 3055865.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA2	NM_001272046.2	c.-9T>A		splice_region_variant	Exon 2 of 14	ENST00000392982.8	NP_001258975.1
VWA2	NM_001272046.2	c.-9T>A		5_prime_UTR_variant	Exon 2 of 14	ENST00000392982.8	NP_001258975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA2	ENST00000392982.8	c.-9T>A		splice_region_variant	Exon 2 of 14	1	NM_001272046.2	ENSP00000376708.3
VWA2	ENST00000392982.8	c.-9T>A		5_prime_UTR_variant	Exon 2 of 14	1	NM_001272046.2	ENSP00000376708.3

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14118 AN: 152030 Hom.: 745 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0627

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.0670

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.0809

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.0726

GnomAD2 exomes AF: 0.0708 AC: 17811 AN: 251482 AF XY: 0.0678

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.0556

Gnomad ASJ exome AF: 0.0481

Gnomad EAS exome AF: 0.0674

Gnomad FIN exome AF: 0.0867

Gnomad NFE exome AF: 0.0748

Gnomad OTH exome AF: 0.0756

GnomAD4 exome AF: 0.0729 AC: 106197 AN: 1455988 Hom.: 4172 Cov.: 30 AF XY: 0.0713 AC XY: 51659 AN XY: 724582

African (AFR) AF: 0.135 AC: 4485 AN: 33274

American (AMR) AF: 0.0558 AC: 2493 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 1309 AN: 26104

East Asian (EAS) AF: 0.0666 AC: 2644 AN: 39670

South Asian (SAS) AF: 0.0344 AC: 2969 AN: 86206

European-Finnish (FIN) AF: 0.0894 AC: 4773 AN: 53400

Middle Eastern (MID) AF: 0.0659 AC: 380 AN: 5764

European-Non Finnish (NFE) AF: 0.0746 AC: 82554 AN: 1106636

Other (OTH) AF: 0.0762 AC: 4590 AN: 60218

GnomAD4 genome AF: 0.0930 AC: 14153 AN: 152148 Hom.: 748 Cov.: 32 AF XY: 0.0917 AC XY: 6819 AN XY: 74396

African (AFR) AF: 0.142 AC: 5903 AN: 41476

American (AMR) AF: 0.0628 AC: 961 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3472

East Asian (EAS) AF: 0.0673 AC: 348 AN: 5170

South Asian (SAS) AF: 0.0354 AC: 171 AN: 4828

European-Finnish (FIN) AF: 0.0809 AC: 857 AN: 10596

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0797 AC: 5421 AN: 67992

Other (OTH) AF: 0.0751 AC: 159 AN: 2116

Alfa AF: 0.0763 Hom.: 362

Bravo AF: 0.0949

EpiCase AF: 0.0704

EpiControl AF: 0.0691

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

VWA2-related disorder Benign:1

Sep 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.75
PhyloP100		0.014
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00057
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.010		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: rs9665610; hg19: chr10-116008464;