2-214436696-C-G

Position:

• chr2-214436696-C-G

Variant summary

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

The NM_001080500.4(VWC2L):​c.458C>G​(p.Ala153Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VWC2L NM_001080500.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

Genes affected

VWC2L (HGNC:37203): (von Willebrand factor C domain containing 2 like) Predicted to be involved in negative regulation of BMP signaling pathway. Predicted to act upstream of or within positive regulation of neuron differentiation. Predicted to be located in extracellular region and synapse. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

VWC2L (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWC2L	NM_001080500.4	c.458C>G	p.Ala153Gly	missense_variant	3/4	ENST00000312504.10	NP_001073969.1
VWC2L	NM_001345929.2	c.390+22113C>G		intron_variant			NP_001332858.1
VWC2L	NR_159945.1	n.1271C>G		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWC2L	ENST00000312504.10	c.458C>G	p.Ala153Gly	missense_variant	3/4	1	NM_001080500.4	ENSP00000308976.5

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

Oct 07, 2024

The c.458C>G (p.A153G) alteration is located in exon 3 (coding exon 2) of the VWC2L gene. This alteration results from a C to G substitution at nucleotide position 458, causing the alanine (A) at amino acid position 153 to be replaced by a glycine (G). 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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.6	L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.025	D
Sift4G	Benign	0.13	T
Polyphen		0.98	D
Vest4		0.69
MutPred		0.52		Loss of stability (P = 0.1029);
MVP		0.28
MPC		1.4
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.23
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-215301420;