10-114248760-C-G

Variant names:

• chr10-114248760-C-G
• rs1032492627
• NM_001272046.2:c.47C>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.47C>G​(p.Ser16Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S16F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VWA2 NM_001272046.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 0 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: 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=0.090714514).

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.47C>G	p.Ser16Cys	missense	Exon 2 of 14	NP_001258975.1	Q5GFL6-1
	VWA2	NM_001320804.1		c.47C>G	p.Ser16Cys	missense	Exon 2 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.47C>G	p.Ser16Cys	missense	Exon 2 of 14	ENSP00000376708.3	Q5GFL6-1
	VWA2	ENST00000603594.2	TSL:2	c.-736C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	ENSP00000473752.2	Q5GFL6-3
	VWA2	ENST00000892505.1		c.47C>G	p.Ser16Cys	missense	Exon 2 of 14	ENSP00000562564.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	10
DANN	Benign	0.96
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.069
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.084
Sift	Benign	0.12	T
Sift4G	Benign	0.15	T
Polyphen		0.21	B
Vest4		0.19
MutPred		0.51		Loss of disorder (P = 0.0448)
MVP		0.32
ClinPred		0.15	T
GERP RS		-0.91
Varity_R		0.082
gMVP		0.50
Mutation Taster		=91/9	polymorphism

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: rs1032492627; hg19: chr10-116008519;