rs34253448

Variant names:

• chr10-114277941-C-A
• NM_001272046.2:c.594C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-114277941-C-A
• chr10-114277941-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001272046.2(VWA2):​c.594C>A​(p.Ser198Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 6.9e-7 (0 hom.)
• Consequence: VWA2 NM_001272046.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA2	NM_001272046.2	c.594C>A	p.Ser198Arg	missense_variant	Exon 7 of 14	ENST00000392982.8	NP_001258975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA2	ENST00000392982.8	c.594C>A	p.Ser198Arg	missense_variant	Exon 7 of 14	1	NM_001272046.2	ENSP00000376708.3
VWA2	ENST00000603594	c.-323C>A		5_prime_UTR_variant	Exon 6 of 11	2		ENSP00000473752.2
VWA2	ENST00000298715.8	n.844C>A		non_coding_transcript_exon_variant	Exon 7 of 12	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458048 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724954

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	8.0
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	0.018
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.43	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.3	H
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.5	D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.58		Loss of glycosylation at S198 (P = 0.1325);
MVP		0.62
ClinPred		0.97	D
GERP RS		-3.3
Varity_R		0.85
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-116037700;