11-61258908-A-G

Position:

• chr11-61258908-A-G

Variant summary

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

The NM_152718.2(VWCE):​c.2635T>C​(p.Ser879Pro) 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. 10/14 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: 0.799

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=0.08462635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWCE	NM_152718.2	c.2635T>C	p.Ser879Pro	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.2635T>C	p.Ser879Pro	missense_variant	20/20	1	NM_152718.2	ENSP00000334186	P1
VWCE	ENST00000301770.10	c.*2032T>C		3_prime_UTR_variant, NMD_transcript_variant	20/20	1		ENSP00000301770
VWCE	ENST00000535710.1	c.1030T>C	p.Ser344Pro	missense_variant	9/9	2		ENSP00000442570

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 06, 2021

The c.2635T>C (p.S879P) alteration is located in exon 20 (coding exon 20) of the VWCE gene. This alteration results from a T to C substitution at nucleotide position 2635, causing the serine (S) at amino acid position 879 to be replaced by a proline (P). 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	0.072
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.0
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.085	T
MutationTaster	Benign	1.0	N;N
Sift4G	Benign	0.34	T
Vest4		0.29
MVP		0.030
ClinPred		0.11	T
GERP RS		1.0

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: chr11-61026380;