NM_001272046.2:c.371+1699G>C

Variant names:

• chr10-114262994-G-C
• rs649785
• NM_001272046.2:c.371+1699G>C

Variant summary

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

The NM_001272046.2(VWA2):​c.371+1699G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,964 control chromosomes in the GnomAD database, including 26,484 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 0.57 (26484 hom., cov: 31)
• Consequence: VWA2 NM_001272046.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA2	NM_001272046.2	MANE Select	c.371+1699G>C		intron	N/A	NP_001258975.1
	VWA2	NM_001320804.1		c.371+1699G>C		intron	N/A	NP_001307733.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA2	ENST00000392982.8	TSL:1 MANE Select	c.371+1699G>C		intron	N/A	ENSP00000376708.3
	VWA2	ENST00000603594.2	TSL:2	c.-546+1699G>C		intron	N/A	ENSP00000473752.2
	VWA2	ENST00000298715.8	TSL:2	n.621+1699G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85960 AN: 151846 Hom.: 26420 Cov.: 31

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.566 AC: 86085 AN: 151964 Hom.: 26484 Cov.: 31 AF XY: 0.556 AC XY: 41332 AN XY: 74274

African (AFR) AF: 0.820 AC: 33994 AN: 41460

American (AMR) AF: 0.527 AC: 8047 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1427 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1034 AN: 5154

South Asian (SAS) AF: 0.316 AC: 1521 AN: 4818

European-Finnish (FIN) AF: 0.467 AC: 4931 AN: 10554

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.492 AC: 33404 AN: 67936

Other (OTH) AF: 0.512 AC: 1078 AN: 2104

Alfa AF: 0.539 Hom.: 3210

Bravo AF: 0.585

Asia WGS AF: 0.331 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		-0.22
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: rs649785; hg19: chr10-116022753;