Genetic Variant ASTN2:c.2807-35674G>C (chr9-116687467-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001365068.1(ASTN2):c.2807-35674G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 132,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000075 ( 0 hom., cov: 21)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ASTN2
NM_001365068.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.68

Publications

1 publications found

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]

ASTN2 links:

TRIM32 (HGNC:16380): (tripartite motif containing 32) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies. The protein has also been localized to the nucleus, where it interacts with the activation domain of the HIV-1 Tat protein. The Tat protein activates transcription of HIV-1 genes. [provided by RefSeq, Jul 2008]

TRIM32 Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive limb-girdle muscular dystrophy type 2H
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
Bardet-Biedl syndrome 11
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TRIM32 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1 link	c.2807-35674G>C		intron_variant	Intron 16 of 22	ENST00000313400.9	NP_001351997.1
TRIM32	NM_012210.4 link	c.-82+86C>G		intron_variant	Intron 1 of 1	ENST00000450136.2	NP_036342.2	Q13049A0A024R843

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9 link	c.2807-35674G>C		intron_variant	Intron 16 of 22	5	NM_001365068.1	ENSP00000314038.4		O75129-1
TRIM32	ENST00000450136.2 link	c.-82+86C>G		intron_variant	Intron 1 of 1	1	NM_012210.4	ENSP00000408292.1		Q13049

Frequencies

GnomAD3 genomes

AF:

0.00000752

AC:

AN:

132948

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000157

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

10466

Hom.:

AF XY:

0.00

AC XY:

AN XY:

5058

African (AFR)

AF:

0.00

AC:

AN:

170

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

192

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

9674

Other (OTH)

AF:

0.00

AC:

AN:

298

GnomAD4 genome

AF:

0.00000752

AC:

AN:

132948

Hom.:

Cov.:

AF XY:

0.0000158

AC XY:

AN XY:

63242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

35874

American (AMR)

AF:

0.00

AC:

AN:

12066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3304

East Asian (EAS)

AF:

0.00

AC:

AN:

3856

South Asian (SAS)

AF:

0.00

AC:

AN:

3604

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.0000157

AC:

AN:

63772

Other (OTH)

AF:

0.00

AC:

AN:

1844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.11

(source)

DANN

Benign

0.68

PhyloP100

-3.7

PromoterAI

-0.026

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

9-116687467-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over