9-116687467-C-T

Variant names:

• chr9-116687467-C-T
• rs112643631
• NM_001365068.1:c.2807-35674G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001365068.1(ASTN2):​c.2807-35674G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0838 in 143,324 control chromosomes in the GnomAD database, including 526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (487 hom., cov: 21)
  • Exomes 𝑓: 0.080 (39 hom.)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.68
• Publications: 1 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-116687467-C-T is Benign according to our data. Variant chr9-116687467-C-T is described in ClinVar as [Benign]. Clinvar id is 1220919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0841 AC: 11173 AN: 132792 Hom.: 485 Cov.: 21

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0865

Gnomad ASJ AF: 0.0609

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0731

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.0797

GnomAD4 exome AF: 0.0805 AC: 841 AN: 10448 Hom.: 39 AF XY: 0.0799 AC XY: 403 AN XY: 5046

African (AFR) AF: 0.0529 AC: 9 AN: 170

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 3 AN: 52

East Asian (EAS) AF: 0.115 AC: 6 AN: 52

South Asian (SAS) AF: 0.0885 AC: 17 AN: 192

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 22

European-Non Finnish (NFE) AF: 0.0804 AC: 776 AN: 9656

Other (OTH) AF: 0.101 AC: 30 AN: 298

GnomAD4 genome AF: 0.0841 AC: 11174 AN: 132876 Hom.: 487 Cov.: 21 AF XY: 0.0871 AC XY: 5507 AN XY: 63244

African (AFR) AF: 0.0498 AC: 1788 AN: 35924

American (AMR) AF: 0.0864 AC: 1044 AN: 12078

Ashkenazi Jewish (ASJ) AF: 0.0609 AC: 201 AN: 3300

East Asian (EAS) AF: 0.154 AC: 592 AN: 3838

South Asian (SAS) AF: 0.109 AC: 391 AN: 3592

European-Finnish (FIN) AF: 0.164 AC: 1227 AN: 7488

Middle Eastern (MID) AF: 0.0798 AC: 19 AN: 238

European-Non Finnish (NFE) AF: 0.0891 AC: 5676 AN: 63698

Other (OTH) AF: 0.0798 AC: 149 AN: 1868

Alfa AF: 0.0369 Hom.: 24

Bravo AF: 0.0768

Asia WGS AF: 0.140 AC: 485 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.17
DANN	Benign	0.91
PhyloP100		-3.7
PromoterAI		0.022	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs112643631; hg19: chr9-119449746; COSMIC: COSV56006515; COSMIC: COSV56006515;