NM_152718.2:c.2662C>G

Variant names:

• chr11-61258881-G-C
• rs142622305
• NM_152718.2:c.2662C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152718.2(VWCE):​c.2662C>G​(p.Pro888Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,367,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P888S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: VWCE NM_152718.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11485046).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152718.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWCE	NM_152718.2	MANE Select	c.2662C>G	p.Pro888Ala	missense	Exon 20 of 20	NP_689931.2	Q96DN2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWCE	ENST00000335613.10	TSL:1 MANE Select	c.2662C>G	p.Pro888Ala	missense	Exon 20 of 20	ENSP00000334186.5	Q96DN2-1
	VWCE	ENST00000301770.10	TSL:1	n.*2059C>G		non_coding_transcript_exon	Exon 20 of 20	ENSP00000301770.6	Q96DN2-2
	VWCE	ENST00000301770.10	TSL:1	n.*2059C>G		3_prime_UTR	Exon 20 of 20	ENSP00000301770.6	Q96DN2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000564 AC: 1 AN: 177262 AF XY: 0.0000107

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000116

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1367770 Hom.: 0 Cov.: 31 AF XY: 0.00000149 AC XY: 1 AN XY: 670540

African (AFR) AF: 0.00 AC: 0 AN: 30210

American (AMR) AF: 0.00 AC: 0 AN: 28968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19882

East Asian (EAS) AF: 0.00 AC: 0 AN: 38912

South Asian (SAS) AF: 0.00 AC: 0 AN: 70150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5322

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1068204

Other (OTH) AF: 0.00 AC: 0 AN: 56252

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000838 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	5.1
DANN	Benign	0.87
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.11	T
PhyloP100		1.5
Sift4G	Benign	0.49	T
Vest4		0.16
MVP		0.030
ClinPred		0.059	T
GERP RS		3.6
Varity_R		0.038
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs142622305; hg19: chr11-61026353;