9-116697564-G-A

Variant names:

• chr9-116697564-G-A
• rs73515229
• NM_001365068.1:c.2806+28207C>T

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.2806+28207C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 762,702 control chromosomes in the GnomAD database, including 613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (417 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (196 hom.)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.560
• Publications: 0 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=-0.85).
• BP6: Variant 9-116697564-G-A is Benign according to our data. Variant chr9-116697564-G-A is described in ClinVar as [Benign]. Clinvar id is 674433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.2806+28207C>T		intron_variant	Intron 16 of 22	ENST00000313400.9	NP_001351997.1
TRIM32	NM_012210.4	c.-81-98G>A		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.2806+28207C>T		intron_variant	Intron 16 of 22	5	NM_001365068.1	ENSP00000314038.4
TRIM32	ENST00000450136.2	c.-81-98G>A		intron_variant	Intron 1 of 1	1	NM_012210.4	ENSP00000408292.1

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6197 AN: 152160 Hom.: 413 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0291

GnomAD4 exome AF: 0.00478 AC: 2915 AN: 610424 Hom.: 196 Cov.: 8 AF XY: 0.00393 AC XY: 1242 AN XY: 316246

African (AFR) AF: 0.143 AC: 2237 AN: 15690

American (AMR) AF: 0.00906 AC: 212 AN: 23390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15828

East Asian (EAS) AF: 0.00 AC: 0 AN: 31490

South Asian (SAS) AF: 0.000428 AC: 22 AN: 51446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29660

Middle Eastern (MID) AF: 0.00774 AC: 18 AN: 2326

European-Non Finnish (NFE) AF: 0.000203 AC: 83 AN: 409310

Other (OTH) AF: 0.0110 AC: 343 AN: 31284

GnomAD4 genome AF: 0.0408 AC: 6216 AN: 152278 Hom.: 417 Cov.: 32 AF XY: 0.0397 AC XY: 2960 AN XY: 74478

African (AFR) AF: 0.142 AC: 5889 AN: 41516

American (AMR) AF: 0.0151 AC: 231 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68030

Other (OTH) AF: 0.0288 AC: 61 AN: 2116

Alfa AF: 0.0194 Hom.: 53

Bravo AF: 0.0467

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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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	-0.85
CADD	Benign	7.2
DANN	Benign	0.55
PhyloP100		0.56
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: rs73515229; hg19: chr9-119459843;