9-116697564-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 0.560

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
ASTN2	NM_001365068.1	c.2806+28207C>T		intron_variant		ENST00000313400.9
TRIM32	NM_012210.4	c.-81-98G>A		intron_variant		ENST00000450136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASTN2	ENST00000313400.9	c.2806+28207C>T		intron_variant		5	NM_001365068.1	A2
TRIM32	ENST00000450136.2	c.-81-98G>A		intron_variant		1	NM_012210.4	P1

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

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.00906

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000428

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000203

Gnomad4 OTH exome AF: 0.0110

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

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0151

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0288

Alfa AF: 0.0182 Hom.: 23

Bravo AF: 0.0467

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.2
Dann	Benign	0.55

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

Other links and lift over

dbSNP: rs73515229; hg19: chr9-119459843;