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GeneBe

10-114286036-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001272046.2(VWA2):c.1095C>T(p.Phe365=) 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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.113
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.113 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VWA2NM_001272046.2 linkuse as main transcriptc.1095C>T p.Phe365= synonymous_variant 11/14 ENST00000392982.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VWA2ENST00000392982.8 linkuse as main transcriptc.1095C>T p.Phe365= synonymous_variant 11/141 NM_001272046.2 P1Q5GFL6-1
VWA2ENST00000603594.2 linkuse as main transcriptc.183C>T p.Phe61= synonymous_variant 10/112 Q5GFL6-3
VWA2ENST00000298715.8 linkuse as main transcriptn.1345C>T non_coding_transcript_exon_variant 11/122

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00382
AC:
582
AN:
152236
Hom.:
2
Cov.:
33
show subpopulations
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
show subpopulations
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
show subpopulations
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00382
AC:
582
AN:
152354
Hom.:
2
Cov.:
33
AF XY:
0.00366
AC XY:
273
AN XY:
74502
show subpopulations
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:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 02, 2018- -

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34495685; hg19: chr10-116045795; API