rs11196686

Variant names:

• chr10-114290249-A-C
• rs11196686
• NM_001272046.2:c.2132A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-114290249-A-C
• chr10-114290249-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001272046.2(VWA2):​c.2132A>C​(p.Gln711Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: VWA2 NM_001272046.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

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]

AFAP1L2 (HGNC:25901): (actin filament associated protein 1 like 2) Enables SH2 domain binding activity; SH3 domain binding activity; and protein tyrosine kinase activator activity. Involved in several processes, including positive regulation of epidermal growth factor receptor signaling pathway; regulation of gene expression; and regulation of mitotic cell cycle. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08748445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA2	NM_001272046.2	c.2132A>C	p.Gln711Pro	missense_variant	Exon 13 of 14	ENST00000392982.8	NP_001258975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA2	ENST00000392982.8	c.2132A>C	p.Gln711Pro	missense_variant	Exon 13 of 14	1	NM_001272046.2	ENSP00000376708.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398228 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689628

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 31600

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 35704

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25178

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 35734

Gnomad4 SAS exome AF: 0.0000126 AC: 1 AN: 79226

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 48172

Gnomad4 NFE exome AF: 0.00 AC: 0 AN: 1078918

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 57998

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	4.9
DANN	Benign	0.97
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.11
Sift	Benign	0.23	T
Sift4G	Benign	0.17	T
Polyphen		0.13	B
Vest4		0.22
MutPred		0.54		Gain of ubiquitination at K710 (P = 0.0575);
MVP		0.61
ClinPred		0.43	T
GERP RS		1.7
Varity_R		0.078
gMVP		0.80
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs11196686; hg19: chr10-116050008;