10-114285997-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001272046.2(VWA2):c.1056G>A(p.Ala352=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00438 in 1,613,772 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (117 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (134 hom.)
• Consequence: VWA2 NM_001272046.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.46

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 10-114285997-G-A is Benign according to our data. Variant chr10-114285997-G-A is described in ClinVar as [Benign]. Clinvar id is 769373.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWA2	NM_001272046.2	c.1056G>A	p.Ala352=	synonymous_variant	11/14	ENST00000392982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWA2	ENST00000392982.8	c.1056G>A	p.Ala352=	synonymous_variant	11/14	1	NM_001272046.2	P1
VWA2	ENST00000603594.2	c.144G>A	p.Ala48=	synonymous_variant	10/11	2
VWA2	ENST00000298715.8	n.1306G>A		non_coding_transcript_exon_variant	11/12	2

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 3438 AN: 152216 Hom.: 117 Cov.: 33

Gnomad AFR AF: 0.0769

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.00589 AC: 1476 AN: 250504 Hom.: 42 AF XY: 0.00433 AC XY: 586 AN XY: 135394

Gnomad AFR exome AF: 0.0794

Gnomad AMR exome AF: 0.00382

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000327

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00248 AC: 3620 AN: 1461438 Hom.: 134 Cov.: 31 AF XY: 0.00214 AC XY: 1559 AN XY: 726966

Gnomad4 AFR exome AF: 0.0823

Gnomad4 AMR exome AF: 0.00490

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000241

Gnomad4 OTH exome AF: 0.00560

GnomAD4 genome AF: 0.0226 AC: 3448 AN: 152334 Hom.: 117 Cov.: 33 AF XY: 0.0217 AC XY: 1620 AN XY: 74494

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0124 Hom.: 42

Bravo AF: 0.0257

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000356

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 20, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	1.5
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs34806476; hg19: chr10-116045756;