1-212972942-C-T

Variant names:

• chr1-212972942-C-T
• rs768463996
• NM_001301056.2:c.860C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001301056.2(VASH2):​c.860C>T​(p.Ala287Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,234 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A287D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: VASH2 NM_001301056.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301056.2. 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
	VASH2	NM_001301056.2	MANE Select	c.860C>T	p.Ala287Val	missense	Exon 6 of 8	NP_001287985.1	Q86V25-1
	VASH2	NM_024749.5		c.728C>T	p.Ala243Val	missense	Exon 4 of 6	NP_079025.2
	VASH2	NM_001136474.3		c.665C>T	p.Ala222Val	missense	Exon 7 of 9	NP_001129946.1	Q86V25-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VASH2	ENST00000517399.3	TSL:1 MANE Select	c.860C>T	p.Ala287Val	missense	Exon 6 of 8	ENSP00000428324.1	Q86V25-1
	VASH2	ENST00000366965.6	TSL:1	c.728C>T	p.Ala243Val	missense	Exon 4 of 6	ENSP00000355932.2	Q86V25-5
	VASH2	ENST00000917486.1		c.1046C>T	p.Ala349Val	missense	Exon 5 of 7	ENSP00000587545.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000801 AC: 2 AN: 249696 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460234 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726512

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0063	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.15	T
Polyphen		0.88	P
Vest4		0.57
MutPred		0.41		Gain of ubiquitination at K285 (P = 0.0825)
MVP		0.23
MPC		0.54
ClinPred		0.78	D
GERP RS		5.4
Varity_R		0.40
gMVP		0.54
Mutation Taster		=45/55	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs768463996; hg19: chr1-213146284; COSMIC: COSV55117602; COSMIC: COSV55117602;