Menu
GeneBe

10-114284966-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001272046.2(VWA2):c.993C>T(p.Asn331=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00436 in 1,596,234 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.023 ( 118 hom., cov: 33)
Exomes 𝑓: 0.0024 ( 130 hom. )

Consequence

VWA2
NM_001272046.2 synonymous

Scores

2
6

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.759
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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 (MetaRNN=0.0018101931).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-114284966-C-T is Benign according to our data. Variant chr10-114284966-C-T is described in ClinVar as [Benign]. Clinvar id is 769372.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=0.759 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VWA2NM_001272046.2 linkuse as main transcriptc.993C>T p.Asn331= synonymous_variant 10/14 ENST00000392982.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VWA2ENST00000392982.8 linkuse as main transcriptc.993C>T p.Asn331= synonymous_variant 10/141 NM_001272046.2 P1Q5GFL6-1
VWA2ENST00000603594.2 linkuse as main transcriptc.77C>T p.Thr26Ile missense_variant 9/112 Q5GFL6-3
VWA2ENST00000298715.8 linkuse as main transcriptn.1243C>T non_coding_transcript_exon_variant 10/122

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0228
AC:
3463
AN:
152194
Hom.:
118
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0774
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0124
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:
0.00571
AC:
1296
AN:
226800
Hom.:
39
AF XY:
0.00420
AC XY:
517
AN XY:
122976
show subpopulations
Gnomad AFR exome
AF:
0.0793
Gnomad AMR exome
AF:
0.00375
Gnomad ASJ exome
AF:
0.000108
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000366
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000289
Gnomad OTH exome
AF:
0.00239
GnomAD4 exome
AF:
0.00241
AC:
3487
AN:
1443922
Hom.:
130
Cov.:
31
AF XY:
0.00211
AC XY:
1512
AN XY:
717380
show subpopulations
Gnomad4 AFR exome
AF:
0.0820
Gnomad4 AMR exome
AF:
0.00488
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000205
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000232
Gnomad4 OTH exome
AF:
0.00551
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0228
AC:
3471
AN:
152312
Hom.:
118
Cov.:
33
AF XY:
0.0219
AC XY:
1634
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.0774
Gnomad4 AMR
AF:
0.0123
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:
0.00682
Hom.:
43
Bravo
AF:
0.0258
ESP6500AA
AF:
0.0781
AC:
344
ESP6500EA
AF:
0.000581
AC:
5
ExAC
?
    Exome Aggregation Consortium database
AF:
0.00694
AC:
843
Asia WGS
AF:
0.00346
AC:
12
AN:
3478

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 testingInvitaeDec 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.36
Cadd
Benign
9.5
Dann
Benign
0.63
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.26
T
MetaRNN
Benign
0.0018
T
MutationTaster
Benign
1.0
D;D
Sift4G
Uncertain
0.028
D
Polyphen
0.36
B
Vest4
0.14
MVP
0.31
GERP RS
5.5

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: rs11817946; hg19: chr10-116044725; API