chr1-212972942-C-A

Position:

• chr1-212972942-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

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/exons	MANE	UniProt
VASH2	NM_001301056.2	c.860C>A	p.Ala287Asp	missense_variant	6/8	ENST00000517399.3
VASH2	NM_024749.5	c.728C>A	p.Ala243Asp	missense_variant	4/6
VASH2	NM_001136474.3	c.665C>A	p.Ala222Asp	missense_variant	7/9
VASH2	NM_001136475.3	c.548C>A	p.Ala183Asp	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VASH2	ENST00000517399.3	c.860C>A	p.Ala287Asp	missense_variant	6/8	1	NM_001301056.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.728C>A (p.A243D) alteration is located in exon 4 (coding exon 3) of the VASH2 gene. This alteration results from a C to A substitution at nucleotide position 728, causing the alanine (A) at amino acid position 243 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D;D;D
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.55	D;D;D;D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.1	.;.;.;.;M
MutationTaster	Benign	0.99	D;D;D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.5	D;D;N;D;N
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D;D;D;D;D
Sift4G	Uncertain	0.050	T;T;D;T;T
Polyphen		0.94, 1.0	.;.;P;.;D
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-213146284;