Variant chr1-212951723-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001301056.2(VASH2):c.181C>T(p.His61Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,605,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

VASH2
NM_001301056.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.51

Variant links:

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]

VASH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11280605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
VASH2	NM_001301056.2 linkuse as main transcript	c.181C>T	p.His61Tyr	missense_variant	2/8	ENST00000517399.3
VASH2	NM_024749.5 linkuse as main transcript	c.181C>T	p.His61Tyr	missense_variant	2/6
VASH2	NM_001136474.3 linkuse as main transcript	c.-15C>T		5_prime_UTR_variant	3/9
VASH2	NM_001136475.3 linkuse as main transcript	c.-37+983C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VASH2	ENST00000517399.3 linkuse as main transcript	c.181C>T	p.His61Tyr	missense_variant	2/8	1	NM_001301056.2	P1	Q86V25-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000431

AC:

AN:

231904

Hom.:

AF XY:

0.00

AC XY:

AN XY:

125322

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000579

Gnomad SAS 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:

6.88e-7

AC:

AN:

1453460

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721880

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2024

The c.181C>T (p.H61Y) alteration is located in exon 2 (coding exon 1) of the VASH2 gene. This alteration results from a C to T substitution at nucleotide position 181, causing the histidine (H) at amino acid position 61 to be replaced by a tyrosine (Y). 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

Benign

0.10

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.049

.;.;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.074

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.69

N;N;N

MutationTaster

Benign

1.0

D;D;D;D;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.75

.;N;N

REVEL

Benign

0.056

Sift

Uncertain

0.024

.;D;D

Sift4G

Uncertain

0.029

D;T;D

Polyphen

0.90

P;P;P

Vest4

0.27

MutPred

0.34

Gain of phosphorylation at H61 (P = 0.0191);Gain of phosphorylation at H61 (P = 0.0191);Gain of phosphorylation at H61 (P = 0.0191);

MVP

0.043

MPC

0.48

ClinPred

0.46

GERP RS

4.7

Varity_R

0.49

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over