chr1-212961215-A-C

Variant summary

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

The NM_001301056.2(VASH2):ā€‹c.326A>Cā€‹(p.Asp109Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,054 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000089 ( 0 hom. )

Consequence

VASH2
NM_001301056.2 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.84
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]

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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=0.22447947).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VASH2NM_001301056.2 linkuse as main transcriptc.326A>C p.Asp109Ala missense_variant 3/8 ENST00000517399.3
VASH2NM_024749.5 linkuse as main transcriptc.326A>C p.Asp109Ala missense_variant 3/6
VASH2NM_001136474.3 linkuse as main transcriptc.131A>C p.Asp44Ala missense_variant 4/9
VASH2NM_001136475.3 linkuse as main transcriptc.14A>C p.Asp5Ala missense_variant 2/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VASH2ENST00000517399.3 linkuse as main transcriptc.326A>C p.Asp109Ala missense_variant 3/81 NM_001301056.2 P1Q86V25-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727244
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1

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 submitterclinical testingAmbry GeneticsDec 06, 2022The c.326A>C (p.D109A) alteration is located in exon 3 (coding exon 2) of the VASH2 gene. This alteration results from a A to C substitution at nucleotide position 326, causing the aspartic acid (D) at amino acid position 109 to be replaced by an alanine (A). 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
0.19
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.071
.;.;.;.;.;T
Eigen
Benign
0.023
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.84
.;T;T;T;T;T
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.22
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.97
.;.;L;L;.;L
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-2.0
N;N;.;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.29
T;T;.;T;D;T
Sift4G
Benign
0.25
T;T;T;T;T;T
Polyphen
0.075, 0.42
.;.;B;B;.;B
Vest4
0.52
MVP
0.12
MPC
0.75
ClinPred
0.81
D
GERP RS
5.0
Varity_R
0.47
gMVP
0.62

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: rs138725158; hg19: chr1-213134557; API