chr2-214477166-C-G

Variant names:

• chr2-214477166-C-G
• rs7604827
• NM_001080500.4:c.520+40408C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080500.4(VWC2L):​c.520+40408C>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: VWC2L NM_001080500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• Publications: 9 publications found

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]

ENSG00000197585 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080500.4. 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
	VWC2L	NM_001080500.4	MANE Select	c.520+40408C>G		intron	N/A	NP_001073969.1	B2RUY7-1
	VWC2L	NM_001345929.2		c.390+62583C>G		intron	N/A	NP_001332858.1	B7ZW27
	VWC2L	NR_159945.1		n.1333+40408C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWC2L	ENST00000312504.10	TSL:1 MANE Select	c.520+40408C>G		intron	N/A	ENSP00000308976.5	B2RUY7-1
	VWC2L	ENST00000427124.1	TSL:1	c.390+62583C>G		intron	N/A	ENSP00000403779.1	B7ZW27
	ENSG00000197585	ENST00000412896.5	TSL:4	n.178-40849G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.78
DANN	Benign	0.46
PhyloP100		-0.082

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: rs7604827; hg19: chr2-215341890;