rs3002288

Variant names:

• chr1-212953223-G-A
• rs3002288
• NM_001301056.2:c.276+1405G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001301056.2(VASH2):​c.276+1405G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 146,732 control chromosomes in the GnomAD database, including 10,916 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 0.36 (10916 hom., cov: 31)
• Consequence: VASH2 NM_001301056.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332
• Publications: 10 publications found

Genes affected

VASH2 (HGNC:25723): (vasohibin 2) Enables actin binding activity; metallocarboxypeptidase activity; and microtubule binding activity. Involved in axon development and proteolysis. Acts upstream of or within cell-cell fusion; positive regulation of angiogenesis; and positive regulation of endothelial cell proliferation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VASH2	NM_001301056.2	c.276+1405G>A		intron_variant	Intron 2 of 7	ENST00000517399.3	NP_001287985.1
VASH2	NM_024749.5	c.276+1405G>A		intron_variant	Intron 2 of 5		NP_079025.2
VASH2	NM_001136474.3	c.81+1405G>A		intron_variant	Intron 3 of 8		NP_001129946.1
VASH2	NM_001136475.3	c.-37+2483G>A		intron_variant	Intron 1 of 6		NP_001129947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VASH2	ENST00000517399.3	c.276+1405G>A		intron_variant	Intron 2 of 7	1	NM_001301056.2	ENSP00000428324.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 52447 AN: 146612 Hom.: 10921 Cov.: 31

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.305

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.357 AC: 52433 AN: 146732 Hom.: 10916 Cov.: 31 AF XY: 0.358 AC XY: 25637 AN XY: 71686

African (AFR) AF: 0.126 AC: 4804 AN: 38030

American (AMR) AF: 0.284 AC: 4195 AN: 14790

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1199 AN: 3426

East Asian (EAS) AF: 0.434 AC: 2213 AN: 5100

South Asian (SAS) AF: 0.480 AC: 2207 AN: 4596

European-Finnish (FIN) AF: 0.438 AC: 4594 AN: 10494

Middle Eastern (MID) AF: 0.299 AC: 83 AN: 278

European-Non Finnish (NFE) AF: 0.475 AC: 31878 AN: 67088

Other (OTH) AF: 0.359 AC: 736 AN: 2048

Alfa AF: 0.304 Hom.: 3332

Bravo AF: 0.322

Asia WGS AF: 0.427 AC: 1482 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.47
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3002288; hg19: chr1-213126565;