rs4673859

Variant names:

• chr2-214552585-G-A
• rs4673859
• NM_001080500.4:c.521-23087G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: Benign. The variant received -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.

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.521-23087G>A		intron	N/A	NP_001073969.1	B2RUY7-1
	VWC2L	NM_001345929.2		c.391-23087G>A		intron	N/A	NP_001332858.1	B7ZW27
	VWC2L	NR_159945.1		n.1483+18440G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWC2L	ENST00000312504.10	TSL:1 MANE Select	c.521-23087G>A		intron	N/A	ENSP00000308976.5	B2RUY7-1
	VWC2L	ENST00000427124.1	TSL:1	c.391-23087G>A		intron	N/A	ENSP00000403779.1	B7ZW27
	ENSG00000197585	ENST00000412896.5	TSL:4	n.178-116268C>T		intron	N/A

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

African (AFR) AF: 0.596 AC: 24728 AN: 41456

American (AMR) AF: 0.811 AC: 12404 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2576 AN: 3472

East Asian (EAS) AF: 0.831 AC: 4290 AN: 5160

South Asian (SAS) AF: 0.804 AC: 3870 AN: 4816

European-Finnish (FIN) AF: 0.796 AC: 8411 AN: 10570

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52513 AN: 67980

Other (OTH) AF: 0.735 AC: 1556 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.010
DANN	Benign	0.33
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs4673859; hg19: chr2-215417309;