10-114286037-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001272046.2(VWA2):c.1096G>A(p.Val366Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,614,142 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (10 hom., cov: 33)
  • Exomes 𝑓: 0.013 (144 hom.)
• Consequence: VWA2 NM_001272046.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.59

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:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010355711).
• BP6: Variant 10-114286037-G-A is Benign according to our data. Variant chr10-114286037-G-A is described in ClinVar as [Benign]. Clinvar id is 774687.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWA2	NM_001272046.2	c.1096G>A	p.Val366Met	missense_variant	11/14	ENST00000392982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWA2	ENST00000392982.8	c.1096G>A	p.Val366Met	missense_variant	11/14	1	NM_001272046.2	P1
VWA2	ENST00000603594.2	c.184G>A	p.Val62Met	missense_variant	10/11	2
VWA2	ENST00000298715.8	n.1346G>A		non_coding_transcript_exon_variant	11/12	2

Frequencies

GnomAD3 genomes AF: 0.00922 AC: 1404 AN: 152232 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.00265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00227

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.0101 AC: 2530 AN: 251214 Hom.: 16 AF XY: 0.0101 AC XY: 1377 AN XY: 135798

Gnomad AFR exome AF: 0.00332

Gnomad AMR exome AF: 0.00630

Gnomad ASJ exome AF: 0.0193

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.00382

Gnomad FIN exome AF: 0.0184

Gnomad NFE exome AF: 0.0129

Gnomad OTH exome AF: 0.0126

GnomAD4 exome AF: 0.0126 AC: 18437 AN: 1461792 Hom.: 144 Cov.: 32 AF XY: 0.0123 AC XY: 8949 AN XY: 727200

Gnomad4 AFR exome AF: 0.00194

Gnomad4 AMR exome AF: 0.00715

Gnomad4 ASJ exome AF: 0.0195

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.00371

Gnomad4 FIN exome AF: 0.0195

Gnomad4 NFE exome AF: 0.0139

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.00922 AC: 1405 AN: 152350 Hom.: 10 Cov.: 33 AF XY: 0.00948 AC XY: 706 AN XY: 74504

Gnomad4 AFR AF: 0.00264

Gnomad4 AMR AF: 0.00784

Gnomad4 ASJ AF: 0.0182

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.0227

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.0124 Hom.: 42

Bravo AF: 0.00836

TwinsUK AF: 0.0146 AC: 54

ALSPAC AF: 0.0143 AC: 55

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.0133 AC: 114

ExAC AF: 0.00934 AC: 1134

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0156

EpiControl AF: 0.0132

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.23
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.024	T;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.94	D;D
MetaRNN	Benign	0.010	T;T
MetaSVM	Uncertain	-0.085	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	0.84	D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.39	N;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.018	D;.
Sift4G	Uncertain	0.045	D;D
Polyphen		0.99	D;P
Vest4		0.40
MPC		0.55
ClinPred		0.024	T
GERP RS		2.7
Varity_R		0.066
gMVP		0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs79009215; hg19: chr10-116045796; COSMIC: COSV100074081; COSMIC: COSV100074081;