Variant 11-61259031-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152718.2(VWCE):c.2512C>T(p.Pro838Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,613,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

VWCE
NM_152718.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

Variant links:

Genes affected

VWCE (HGNC:26487): (von Willebrand factor C and EGF domains) Predicted to enable calcium ion binding activity. Involved in cellular response to virus. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

VWCE links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12571284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWCE	NM_152718.2 linkuse as main transcript	c.2512C>T	p.Pro838Ser	missense_variant	20/20	ENST00000335613.10	NP_689931.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWCE	ENST00000335613.10 linkuse as main transcript	c.2512C>T	p.Pro838Ser	missense_variant	20/20	1	NM_152718.2	ENSP00000334186	P1	Q96DN2-1
VWCE	ENST00000301770.10 linkuse as main transcript	c.*1909C>T		3_prime_UTR_variant, NMD_transcript_variant	20/20	1		ENSP00000301770		Q96DN2-2
VWCE	ENST00000535710.1 linkuse as main transcript	c.907C>T	p.Pro303Ser	missense_variant	9/9	2		ENSP00000442570
VWCE	ENST00000538438.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000679

AC:

AN:

250478

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

135484

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000121

AC:

177

AN:

1461622

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000150

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000125

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000113

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.2512C>T (p.P838S) alteration is located in exon 20 (coding exon 20) of the VWCE gene. This alteration results from a C to T substitution at nucleotide position 2512, causing the proline (P) at amino acid position 838 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

T;T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.63

T;T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.5

.;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.1

.;D;D

REVEL

Benign

0.035

Sift

Pathogenic

0.0

.;D;D

Sift4G

Benign

0.41

T;T;T

Polyphen

0.42

.;B;.

Vest4

0.12

MVP

0.40

MPC

0.33

ClinPred

0.13

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.088

gMVP

0.36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over