chr2-214477166-C-T

Position:

• chr2-214477166-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080500.4(VWC2L):​c.520+40408C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,224 control chromosomes in the GnomAD database, including 51,807 homozygotes. 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: 𝑓 0.82 (51807 hom., cov: 33)
• Consequence: VWC2L NM_001080500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWC2L	NM_001080500.4	c.520+40408C>T		intron_variant		ENST00000312504.10	NP_001073969.1
VWC2L	NM_001345929.2	c.390+62583C>T		intron_variant			NP_001332858.1
VWC2L	NR_159945.1	n.1333+40408C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWC2L	ENST00000312504.10	c.520+40408C>T		intron_variant		1	NM_001080500.4	ENSP00000308976	P1
	ENST00000412896.5	n.178-40849G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124448 AN: 152106 Hom.: 51779 Cov.: 33

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.942

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.836

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

GnomAD4 genome AF: 0.818 AC: 124522 AN: 152224 Hom.: 51807 Cov.: 33 AF XY: 0.822 AC XY: 61211 AN XY: 74424

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.886

Gnomad4 ASJ AF: 0.894

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.866

Gnomad4 OTH AF: 0.837

Alfa AF: 0.848 Hom.: 26272

Bravo AF: 0.813

Asia WGS AF: 0.939 AC: 3265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.87
DANN	Benign	0.43

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

LitVar

Other links and lift over

dbSNP: rs7604827; hg19: chr2-215341890;