NM_001301056.2:c.139G>A

Variant names:

• chr1-212951681-G-A
• rs751957489
• NM_001301056.2:c.139G>A

Variant summary

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

The NM_001301056.2(VASH2):​c.139G>A​(p.Val47Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000346 in 1,446,706 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. V47L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: VASH2 NM_001301056.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.94
• 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]

ENSG00000306165 (HGNC:):

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.139G>A	p.Val47Met	missense	Exon 2 of 8	NP_001287985.1	Q86V25-1
	VASH2	NM_001136474.3		c.-57G>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 9	NP_001129946.1	Q86V25-2
	VASH2	NM_024749.5		c.139G>A	p.Val47Met	missense	Exon 2 of 6	NP_079025.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VASH2	ENST00000517399.3	TSL:1 MANE Select	c.139G>A	p.Val47Met	missense	Exon 2 of 8	ENSP00000428324.1	Q86V25-1
	VASH2	ENST00000366965.6	TSL:1	c.139G>A	p.Val47Met	missense	Exon 2 of 6	ENSP00000355932.2	Q86V25-5
	VASH2	ENST00000366966.6	TSL:5	c.-57G>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 9	ENSP00000430319.1	Q86V25-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000908 AC: 2 AN: 220374 AF XY: 0.00000840

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000202

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1446706 Hom.: 0 Cov.: 33 AF XY: 0.00000279 AC XY: 2 AN XY: 717832

African (AFR) AF: 0.00 AC: 0 AN: 33370

American (AMR) AF: 0.00 AC: 0 AN: 41784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25756

East Asian (EAS) AF: 0.00 AC: 0 AN: 39128

South Asian (SAS) AF: 0.00 AC: 0 AN: 83172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000452 AC: 5 AN: 1105974

Other (OTH) AF: 0.00 AC: 0 AN: 59866

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.079	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.9
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.45
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.022	D
Polyphen		0.99	D
Vest4		0.46
MutPred		0.33		Gain of sheet (P = 0.039)
MVP		0.093
MPC		0.79
ClinPred		0.84	D
GERP RS		2.5
Varity_R		0.097
gMVP		0.47
Mutation Taster		=79/21	polymorphism

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: rs751957489; hg19: chr1-213125023;