rs34495685

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-114286036-C-T
• chr10-114286036-C-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

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

Our verdict: Benign. The variant received -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 VariationId 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

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.1095C>T	p.Phe365Phe	synonymous	Exon 11 of 14	NP_001258975.1	Q5GFL6-1
	VWA2	NM_001320804.1		c.1095C>T	p.Phe365Phe	synonymous	Exon 11 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.1095C>T	p.Phe365Phe	synonymous	Exon 11 of 14	ENSP00000376708.3	Q5GFL6-1
	VWA2	ENST00000892505.1		c.1095C>T	p.Phe365Phe	synonymous	Exon 11 of 14	ENSP00000562564.1
	VWA2	ENST00000942547.1		c.1095C>T	p.Phe365Phe	synonymous	Exon 11 of 13	ENSP00000612606.1

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

GnomAD2 exomes AF: 0.00451 AC: 1132 AN: 251226 AF XY: 0.00514

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 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

African (AFR) AF: 0.000448 AC: 15 AN: 33480

American (AMR) AF: 0.00159 AC: 71 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 264 AN: 26136

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.0102 AC: 883 AN: 86252

European-Finnish (FIN) AF: 0.000394 AC: 21 AN: 53360

Middle Eastern (MID) AF: 0.00884 AC: 51 AN: 5768

European-Non Finnish (NFE) AF: 0.00501 AC: 5575 AN: 1111996

Other (OTH) AF: 0.00584 AC: 353 AN: 60396

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

African (AFR) AF: 0.00111 AC: 46 AN: 41594

American (AMR) AF: 0.00353 AC: 54 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00979 AC: 34 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4824

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00559 AC: 380 AN: 68036

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	5.0
DANN	Benign	0.70
PhyloP100		0.11
Mutation Taster		=100/0	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: rs34495685; hg19: chr10-116045795;