2-214568841-A-T

Variant names:

• chr2-214568841-A-T
• rs6435833
• NM_001080500.4:c.521-6831A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080500.4(VWC2L):​c.521-6831A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,874 control chromosomes in the GnomAD database, including 8,549 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 0.31 (8549 hom., cov: 31)
• Consequence: VWC2L NM_001080500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWC2L	NM_001080500.4	c.521-6831A>T		intron_variant	Intron 3 of 3	ENST00000312504.10	NP_001073969.1
VWC2L	NM_001345929.2	c.391-6831A>T		intron_variant	Intron 2 of 2		NP_001332858.1
VWC2L	NR_159945.1	n.1484-6831A>T		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWC2L	ENST00000312504.10	c.521-6831A>T		intron_variant	Intron 3 of 3	1	NM_001080500.4	ENSP00000308976.5
VWC2L	ENST00000427124.1	c.391-6831A>T		intron_variant	Intron 2 of 2	1		ENSP00000403779.1
ENSG00000197585	ENST00000412896.5	n.177+114241T>A		intron_variant	Intron 2 of 3	4
ENSG00000197585	ENST00000437883.1	n.133-95072T>A		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46646 AN: 151758 Hom.: 8550 Cov.: 31

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.307 AC: 46678 AN: 151874 Hom.: 8549 Cov.: 31 AF XY: 0.301 AC XY: 22339 AN XY: 74230

African (AFR) AF: 0.525 AC: 21746 AN: 41388

American (AMR) AF: 0.232 AC: 3544 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 878 AN: 3470

East Asian (EAS) AF: 0.187 AC: 964 AN: 5160

South Asian (SAS) AF: 0.197 AC: 948 AN: 4806

European-Finnish (FIN) AF: 0.205 AC: 2156 AN: 10538

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15426 AN: 67946

Other (OTH) AF: 0.293 AC: 617 AN: 2108

Alfa AF: 0.267 Hom.: 779

Bravo AF: 0.323

Asia WGS AF: 0.194 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.62
PhyloP100		0.046
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: rs6435833; hg19: chr2-215433565;