chr2-214552585-G-A

Position:

• chr2-214552585-G-A

Variant summary

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

The NM_001080500.4(VWC2L):​c.521-23087G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,062 control chromosomes in the GnomAD database, including 41,163 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 0.73 (41163 hom., cov: 31)
• Consequence: VWC2L NM_001080500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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 = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWC2L	NM_001080500.4	c.521-23087G>A		intron_variant		ENST00000312504.10	NP_001073969.1
VWC2L	NM_001345929.2	c.391-23087G>A		intron_variant			NP_001332858.1
VWC2L	NR_159945.1	n.1483+18440G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWC2L	ENST00000312504.10	c.521-23087G>A		intron_variant		1	NM_001080500.4	ENSP00000308976	P1
VWC2L	ENST00000427124.1	c.391-23087G>A		intron_variant		1		ENSP00000403779
	ENST00000412896.5	n.178-116268C>T		intron_variant, non_coding_transcript_variant		4
	ENST00000437883.1	n.133-78816C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111066 AN: 151944 Hom.: 41132 Cov.: 31

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.731 AC: 111149 AN: 152062 Hom.: 41163 Cov.: 31 AF XY: 0.736 AC XY: 54731 AN XY: 74328

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.735

Alfa AF: 0.744 Hom.: 7937

Bravo AF: 0.725

Asia WGS AF: 0.811 AC: 2821 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	0.010
DANN	Benign	0.33

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: rs4673859; hg19: chr2-215417309;