rs597371

Positions:

• chr10-114272760-A-G
• chr10-114272760-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001272046.2(VWA2):​c.392A>G​(p.Glu131Gly) variant causes a missense change. The variant allele was found at a frequency of 0.459 in 1,608,198 control chromosomes in the GnomAD database, including 175,882 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.54 (24650 hom., cov: 31)
  • Exomes 𝑓: 0.45 (151232 hom.)
• Consequence: VWA2 NM_001272046.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.39

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.222377E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWA2	NM_001272046.2	c.392A>G	p.Glu131Gly	missense_variant	6/14	ENST00000392982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWA2	ENST00000392982.8	c.392A>G	p.Glu131Gly	missense_variant	6/14	1	NM_001272046.2	P1
VWA2	ENST00000603594.2	c.-525A>G		5_prime_UTR_variant	5/11	2
VWA2	ENST00000298715.8	n.642A>G		non_coding_transcript_exon_variant	6/12	2

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82428 AN: 151682 Hom.: 24589 Cov.: 31

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.484

GnomAD3 exomes AF: 0.466 AC: 115605 AN: 248288 Hom.: 28332 AF XY: 0.460 AC XY: 61694 AN XY: 134226

Gnomad AFR exome AF: 0.816

Gnomad AMR exome AF: 0.480

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.344

Gnomad SAS exome AF: 0.525

Gnomad FIN exome AF: 0.410

Gnomad NFE exome AF: 0.436

Gnomad OTH exome AF: 0.444

GnomAD4 exome AF: 0.451 AC: 656278 AN: 1456398 Hom.: 151232 Cov.: 39 AF XY: 0.451 AC XY: 326299 AN XY: 723944

Gnomad4 AFR exome AF: 0.829

Gnomad4 AMR exome AF: 0.477

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.365

Gnomad4 SAS exome AF: 0.522

Gnomad4 FIN exome AF: 0.416

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.454

GnomAD4 genome AF: 0.544 AC: 82550 AN: 151800 Hom.: 24650 Cov.: 31 AF XY: 0.538 AC XY: 39914 AN XY: 74166

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.484

Alfa AF: 0.451 Hom.: 39846

Bravo AF: 0.558

TwinsUK AF: 0.446 AC: 1652

ALSPAC AF: 0.469 AC: 1809

ESP6500AA AF: 0.800 AC: 3526

ESP6500EA AF: 0.430 AC: 3700

ExAC AF: 0.475 AC: 57736

Asia WGS AF: 0.502 AC: 1747 AN: 3478

EpiCase AF: 0.421

EpiControl AF: 0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.036
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.075
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.087	T
MetaRNN	Benign	6.2e-7	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-3.7	N
MutationTaster	Benign	0.97	P;P
PrimateAI	Benign	0.40	T
PROVEAN	Benign	5.9	N
REVEL	Benign	0.22
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.039
ClinPred		0.0032	T
GERP RS		4.3
Varity_R		0.045
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs597371; hg19: chr10-116032519; COSMIC: COSV53905887;