1-212972851-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001301056.2(VASH2):​c.769C>T​(p.His257Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

VASH2
NM_001301056.2 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.74
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.756

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VASH2NM_001301056.2 linkc.769C>T p.His257Tyr missense_variant Exon 6 of 8 ENST00000517399.3 NP_001287985.1 Q86V25-1A8K4K8
VASH2NM_024749.5 linkc.637C>T p.His213Tyr missense_variant Exon 4 of 6 NP_079025.2 Q86V25-5A8K4K8
VASH2NM_001136474.3 linkc.574C>T p.His192Tyr missense_variant Exon 7 of 9 NP_001129946.1 Q86V25-2A0A140VJZ5A8K4K8
VASH2NM_001136475.3 linkc.457C>T p.His153Tyr missense_variant Exon 5 of 7 NP_001129947.1 Q86V25-6A8K4K8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VASH2ENST00000517399.3 linkc.769C>T p.His257Tyr missense_variant Exon 6 of 8 1 NM_001301056.2 ENSP00000428324.1 Q86V25-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251418
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000712
Hom.:
0
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
Aug 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.637C>T (p.H213Y) alteration is located in exon 4 (coding exon 3) of the VASH2 gene. This alteration results from a C to T substitution at nucleotide position 637, causing the histidine (H) at amino acid position 213 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
Uncertain
0.44
BayesDel_addAF
Uncertain
0.075
D
BayesDel_noAF
Uncertain
0.050
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.42
.;.;.;.;T
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.95
.;D;D;D;D
M_CAP
Benign
0.0046
T
MetaRNN
Pathogenic
0.76
D;D;D;D;D
MetaSVM
Benign
-0.45
T
MutationAssessor
Uncertain
2.3
.;.;.;.;M
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-3.5
D;D;D;D;D
REVEL
Uncertain
0.60
Sift
Benign
0.077
T;T;T;T;T
Sift4G
Benign
0.21
T;T;D;T;T
Polyphen
0.99, 1.0
.;.;D;.;D
Vest4
0.81
MutPred
0.43
.;.;.;.;Loss of disorder (P = 0.0503);
MVP
0.15
MPC
1.1
ClinPred
0.90
D
GERP RS
5.3
Varity_R
0.66
gMVP
0.59

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

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

Other links and lift over

dbSNP: rs1243433850; hg19: chr1-213146193; API