11-61258724-G-C

Position:

• chr11-61258724-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152718.2(VWCE):​c.2819C>G​(p.Pro940Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VWCE NM_152718.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15

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]

ACMG classification

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=0.24021837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWCE	NM_152718.2	c.2819C>G	p.Pro940Arg	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	c.2819C>G	p.Pro940Arg	missense_variant	20/20	1	NM_152718.2	ENSP00000334186	P1
VWCE	ENST00000301770.10	c.*2216C>G		3_prime_UTR_variant, NMD_transcript_variant	20/20	1		ENSP00000301770
VWCE	ENST00000535710.1	c.1214C>G	p.Pro405Arg	missense_variant	9/9	2		ENSP00000442570

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 06, 2024

The c.2819C>G (p.P940R) alteration is located in exon 20 (coding exon 20) of the VWCE gene. This alteration results from a C to G substitution at nucleotide position 2819, causing the proline (P) at amino acid position 940 to be replaced by an arginine (R). 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	0.068
BayesDel_addAF	Benign	0.0093	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T;T;T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.55	T;T;T
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.69	.;N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.5	.;N;N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	.;D;D
Sift4G	Benign	0.15	T;T;T
Polyphen		0.74	.;P;.
Vest4		0.22
MutPred		0.13		.;Loss of glycosylation at P940 (P = 0.0319);.;
MVP		0.68
MPC		0.56
ClinPred		0.40	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.059
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-61026196;