NM_001301056.2:c.860C>A

Variant names:

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

Variant summary

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

The NM_001301056.2(VASH2):​c.860C>A​(p.Ala287Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VASH2 NM_001301056.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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>A	p.Ala287Asp	missense	Exon 6 of 8	NP_001287985.1	Q86V25-1
	VASH2	NM_024749.5		c.728C>A	p.Ala243Asp	missense	Exon 4 of 6	NP_079025.2
	VASH2	NM_001136474.3		c.665C>A	p.Ala222Asp	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>A	p.Ala287Asp	missense	Exon 6 of 8	ENSP00000428324.1	Q86V25-1
	VASH2	ENST00000366965.6	TSL:1	c.728C>A	p.Ala243Asp	missense	Exon 4 of 6	ENSP00000355932.2	Q86V25-5
	VASH2	ENST00000917486.1		c.1046C>A	p.Ala349Asp	missense	Exon 5 of 7	ENSP00000587545.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.7
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.050	T
Polyphen		0.94	P
Vest4		0.70
MutPred		0.43		Loss of helix (P = 0.0376)
MVP		0.25
MPC		0.85
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.73
gMVP		0.76
Mutation Taster		=29/71	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;