chr9-116697371-A-G

Variant names:

• chr9-116697371-A-G
• rs114597839
• NM_001365068.1:c.2806+28400T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001365068.1(ASTN2):​c.2806+28400T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 289,224 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0082 (21 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (1 hom.)
• Consequence: ASTN2 NM_001365068.1 intron
• Scores: Splicing: ADA: 0.3886
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.638
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 9-116697371-A-G is Benign according to our data. Variant chr9-116697371-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1188514.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00816 (1243/152320) while in subpopulation AFR AF = 0.0289 (1202/41576). AF 95% confidence interval is 0.0276. There are 21 homozygotes in GnomAd4. There are 582 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1243 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.2806+28400T>C		intron_variant	Intron 16 of 22	ENST00000313400.9	NP_001351997.1
TRIM32	NM_012210.4	c.-81-291A>G		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+28400T>C		intron_variant	Intron 16 of 22	5	NM_001365068.1	ENSP00000314038.4
TRIM32	ENST00000450136.2	c.-81-291A>G		intron_variant	Intron 1 of 1	1	NM_012210.4	ENSP00000408292.1

Frequencies

GnomAD3 genomes AF: 0.00816 AC: 1242 AN: 152202 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.00146 AC: 200 AN: 136904 Hom.: 1 Cov.: 0 AF XY: 0.00124 AC XY: 89 AN XY: 72062

African (AFR) AF: 0.0365 AC: 178 AN: 4882

American (AMR) AF: 0.00217 AC: 14 AN: 6438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3596

East Asian (EAS) AF: 0.00 AC: 0 AN: 7182

South Asian (SAS) AF: 0.00 AC: 0 AN: 19896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 528

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 81352

Other (OTH) AF: 0.00111 AC: 8 AN: 7238

GnomAD4 genome AF: 0.00816 AC: 1243 AN: 152320 Hom.: 21 Cov.: 32 AF XY: 0.00781 AC XY: 582 AN XY: 74484

African (AFR) AF: 0.0289 AC: 1202 AN: 41576

American (AMR) AF: 0.00150 AC: 23 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68030

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.0110 Hom.: 3

Bravo AF: 0.00931

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 02, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.8
DANN	Benign	0.96
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.39
dbscSNV1_RF	Pathogenic	0.73
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: rs114597839; hg19: chr9-119459650;