11-61258766-G-A

Variant names:

• chr11-61258766-G-A
• NM_152718.2:c.2777C>T

Variant summary

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

The NM_152718.2(VWCE):​c.2777C>T​(p.Ser926Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S926P) has been classified 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: 3.82

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=0.25884563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWCE	NM_152718.2	c.2777C>T	p.Ser926Phe	missense_variant	Exon 20 of 20	ENST00000335613.10	NP_689931.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWCE	ENST00000335613.10	c.2777C>T	p.Ser926Phe	missense_variant	Exon 20 of 20	1	NM_152718.2	ENSP00000334186.5
VWCE	ENST00000301770.10	n.*2174C>T		non_coding_transcript_exon_variant	Exon 20 of 20	1		ENSP00000301770.6
VWCE	ENST00000301770.10	n.*2174C>T		3_prime_UTR_variant	Exon 20 of 20	1		ENSP00000301770.6
VWCE	ENST00000535710.1	c.1172C>T	p.Ser391Phe	missense_variant	Exon 9 of 9	2		ENSP00000442570.1

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

Oct 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2777C>T (p.S926F) 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 2777, causing the serine (S) at amino acid position 926 to be replaced by a phenylalanine (F). 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	0.17
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T;T;T
Eigen	Benign	0.035
Eigen_PC	Benign	-0.043
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.67	T;T;T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.0	.;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	.;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0020	.;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.86	.;P;.
Vest4		0.18
MutPred		0.25		.;Loss of glycosylation at S926 (P = 0.0059);.;
MVP		0.45
MPC		0.54
ClinPred		0.76	D
GERP RS		3.8
Varity_R		0.079
gMVP		0.27

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: chr11-61026238;