chr9-116487369-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001365068.1(ASTN2):​c.3487G>A​(p.Gly1163Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 0.0000096 ( 0 hom. )

Consequence

ASTN2
NM_001365068.1 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.29
Variant links:
Genes affected
ASTN2 (HGNC:17021): (astrotactin 2) This gene encodes a protein that is expressed in the brain and may function in neuronal migration, based on functional studies of the related astrotactin 1 gene in human and mouse. A deletion at this locus has been associated with schizophrenia. Multiple transcript variants encoding different proteins have been found for this locus. [provided by RefSeq, May 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.041909963).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASTN2NM_001365068.1 linkc.3487G>A p.Gly1163Ser missense_variant Exon 20 of 23 ENST00000313400.9 NP_001351997.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASTN2ENST00000313400.9 linkc.3487G>A p.Gly1163Ser missense_variant Exon 20 of 23 5 NM_001365068.1 ENSP00000314038.4 O75129-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152118
Hom.:
0
Cov.:
32
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:
0.000579
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:
0.0000478
AC:
12
AN:
251060
Hom.:
0
AF XY:
0.0000516
AC XY:
7
AN XY:
135652
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000490
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461624
Hom.:
0
Cov.:
30
AF XY:
0.00000963
AC XY:
7
AN XY:
727110
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152118
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000579
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.0000576
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 05, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3334G>A (p.G1112S) alteration is located in exon 19 (coding exon 19) of the ASTN2 gene. This alteration results from a G to A substitution at nucleotide position 3334, causing the glycine (G) at amino acid position 1112 to be replaced by a serine (S). 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
0.061
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
20
DANN
Benign
0.93
DEOGEN2
Benign
0.013
T;.;.;.;.;.
Eigen
Benign
-0.23
Eigen_PC
Benign
0.042
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.82
T;T;T;T;T;T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.042
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.46
N;.;.;.;.;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
0.41
N;N;N;N;N;N
REVEL
Benign
0.054
Sift
Benign
0.58
T;T;T;T;T;T
Sift4G
Benign
0.88
T;T;T;T;T;T
Polyphen
0.18
B;B;B;.;B;B
Vest4
0.21
MutPred
0.27
Loss of methylation at K1166 (P = 0.1126);.;.;.;.;.;
MVP
0.043
MPC
0.23
ClinPred
0.061
T
GERP RS
5.5
Varity_R
0.30
gMVP
0.39

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: rs765621808; hg19: chr9-119249648; API