rs141503948

Variant names:

• chr10-114278756-G-A
• rs141503948
• NM_001272046.2:c.738G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-114278756-G-A
• chr10-114278756-G-C
• chr10-114278756-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_001272046.2(VWA2):​c.738G>A​(p.Thr246Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,613,920 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0090 (13 hom., cov: 32)
  • Exomes 𝑓: 0.013 (157 hom.)
• Consequence: VWA2 NM_001272046.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.49
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 10-114278756-G-A is Benign according to our data. Variant chr10-114278756-G-A is described in ClinVar as Benign. ClinVar VariationId is 3042390.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0133 (19388/1461592) while in subpopulation NFE AF = 0.0157 (17416/1112010). AF 95% confidence interval is 0.0155. There are 157 homozygotes in GnomAdExome4. There are 9375 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001272046.2. 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
	VWA2	NM_001272046.2	MANE Select	c.738G>A	p.Thr246Thr	synonymous	Exon 8 of 14	NP_001258975.1	Q5GFL6-1
	VWA2	NM_001320804.1		c.738G>A	p.Thr246Thr	synonymous	Exon 8 of 14	NP_001307733.1	Q5GFL6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA2	ENST00000392982.8	TSL:1 MANE Select	c.738G>A	p.Thr246Thr	synonymous	Exon 8 of 14	ENSP00000376708.3	Q5GFL6-1
	VWA2	ENST00000892505.1		c.738G>A	p.Thr246Thr	synonymous	Exon 8 of 14	ENSP00000562564.1
	VWA2	ENST00000942547.1		c.738G>A	p.Thr246Thr	synonymous	Exon 8 of 13	ENSP00000612606.1

Frequencies

GnomAD3 genomes AF: 0.00906 AC: 1379 AN: 152210 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00260

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.00479

GnomAD2 exomes AF: 0.00962 AC: 2416 AN: 251180 AF XY: 0.00988

Gnomad AFR exome AF: 0.00308

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0194

Gnomad NFE exome AF: 0.0154

Gnomad OTH exome AF: 0.00701

GnomAD4 exome AF: 0.0133 AC: 19388 AN: 1461592 Hom.: 157 Cov.: 32 AF XY: 0.0129 AC XY: 9375 AN XY: 727088

African (AFR) AF: 0.00209 AC: 70 AN: 33470

American (AMR) AF: 0.00271 AC: 121 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000383 AC: 10 AN: 26136

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39700

South Asian (SAS) AF: 0.00215 AC: 185 AN: 86246

European-Finnish (FIN) AF: 0.0189 AC: 1010 AN: 53372

Middle Eastern (MID) AF: 0.000720 AC: 4 AN: 5556

European-Non Finnish (NFE) AF: 0.0157 AC: 17416 AN: 1112010

Other (OTH) AF: 0.00932 AC: 563 AN: 60378

GnomAD4 genome AF: 0.00904 AC: 1377 AN: 152328 Hom.: 13 Cov.: 32 AF XY: 0.00888 AC XY: 661 AN XY: 74470

African (AFR) AF: 0.00260 AC: 108 AN: 41590

American (AMR) AF: 0.00202 AC: 31 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4820

European-Finnish (FIN) AF: 0.0203 AC: 216 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0147 AC: 1000 AN: 68022

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.0120 Hom.: 8

Bravo AF: 0.00750

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0124

EpiControl AF: 0.0119

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	VWA2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.33
DANN	Benign	0.55
PhyloP100		-1.5
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs141503948; hg19: chr10-116038515;