rs751957489

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-212951681-G-A
• chr1-212951681-G-C
• chr1-212951681-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001136474.3(VASH2):​c.-57G>A variant causes a 5 prime UTR premature start codon gain 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: VASH2 NM_001136474.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.94

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VASH2	NM_001301056.2	c.139G>A	p.Val47Met	missense_variant	Exon 2 of 8	ENST00000517399.3	NP_001287985.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VASH2	ENST00000517399.3	c.139G>A	p.Val47Met	missense_variant	Exon 2 of 8	1	NM_001301056.2	ENSP00000428324.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000908 AC: 2 AN: 220374 Hom.: 0 AF XY: 0.00000840 AC XY: 1 AN XY: 119012

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000452

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D
M_CAP	Benign	0.079	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.4	M;M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.3	.;N;N
REVEL	Uncertain	0.45
Sift	Uncertain	0.0050	.;D;D
Sift4G	Uncertain	0.022	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.46
MutPred		0.33		Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs751957489; hg19: chr1-213125023;