NM_001272046.2:c.1095C>T

Variant names:

• chr10-114286036-C-T
• rs34495685
• NM_001272046.2:c.1095C>T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001272046.2(VWA2):​c.1095C>T​(p.Phe365Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00485 in 1,614,166 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0050 (35 hom.)
• Consequence: VWA2 NM_001272046.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.113

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 10-114286036-C-T is Benign according to our data. Variant chr10-114286036-C-T is described in ClinVar as [Benign]. Clinvar id is 778416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.113 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA2	NM_001272046.2	c.1095C>T	p.Phe365Phe	synonymous_variant	Exon 11 of 14	ENST00000392982.8	NP_001258975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA2	ENST00000392982.8	c.1095C>T	p.Phe365Phe	synonymous_variant	Exon 11 of 14	1	NM_001272046.2	ENSP00000376708.3
VWA2	ENST00000603594.2	c.183C>T	p.Phe61Phe	synonymous_variant	Exon 10 of 11	2		ENSP00000473752.2
VWA2	ENST00000298715.8	n.1345C>T		non_coding_transcript_exon_variant	Exon 11 of 12	2

Frequencies

GnomAD3 genomes AF: 0.00382 AC: 582 AN: 152236 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00558

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00451 AC: 1132 AN: 251226 Hom.: 9 AF XY: 0.00514 AC XY: 698 AN XY: 135804

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.00982

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0101

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00534

Gnomad OTH exome AF: 0.00652

GnomAD4 exome AF: 0.00495 AC: 7239 AN: 1461812 Hom.: 35 Cov.: 31 AF XY: 0.00526 AC XY: 3823 AN XY: 727202

Gnomad4 AFR exome AF: 0.000448

Gnomad4 AMR exome AF: 0.00159

Gnomad4 ASJ exome AF: 0.0101

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.0102

Gnomad4 FIN exome AF: 0.000394

Gnomad4 NFE exome AF: 0.00501

Gnomad4 OTH exome AF: 0.00584

GnomAD4 genome AF: 0.00382 AC: 582 AN: 152354 Hom.: 2 Cov.: 33 AF XY: 0.00366 AC XY: 273 AN XY: 74502

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00559

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00476 Hom.: 0

Bravo AF: 0.00372

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.00643

EpiControl AF: 0.00557

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

VWA2: BP4, BP7, BS1, BS2 -

May 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	5.0
DANN	Benign	0.70

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: rs34495685; hg19: chr10-116045795;