Genetic Variant AUTS2:p.His1132_His1133dup (chr7-70790590-G-GCCACCA) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_015570.4(AUTS2):c.3395_3400dupACCACC(p.His1132_His1133dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,600,798 control chromosomes in the GnomAD database, including 187 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 160 hom. )

Consequence

AUTS2
NM_015570.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.930

Variant links:

Genes affected

AUTS2 (HGNC:14262): (activator of transcription and developmental regulator AUTS2) This gene has been implicated in neurodevelopment and as a candidate gene for numerous neurological disorders, including autism spectrum disorders, intellectual disability, and developmental delay. Mutations in this gene have also been associated with non-neurological disorders, such as acute lymphoblastic leukemia, aging of the skin, early-onset androgenetic alopecia, and certain cancers. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2014]

AUTS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-70790590-G-GCCACCA is Benign according to our data. Variant chr7-70790590-G-GCCACCA is described in ClinVar as [Benign]. Clinvar id is 445607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4 link	c.3395_3400dupACCACC	p.His1132_His1133dup	disruptive_inframe_insertion	Exon 19 of 19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10 link	c.3395_3400dupACCACC	p.His1132_His1133dup	disruptive_inframe_insertion	Exon 19 of 19	1	NM_015570.4	ENSP00000344087.4		Q8WXX7-1

Frequencies

GnomAD3 genomes

AF:

0.00527

AC:

800

AN:

151768

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0725

Gnomad SAS

AF:

0.0397

Gnomad FIN

AF:

0.00274

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.00624

GnomAD3 exomes

AF:

0.0102

AC:

1936

AN:

189948

Hom.:

AF XY:

0.0109

AC XY:

1126

AN XY:

103280

show subpopulations

Gnomad AFR exome

AF:

0.000975

Gnomad AMR exome

AF:

0.00216

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.0650

Gnomad SAS exome

AF:

0.0311

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.00905

GnomAD4 exome

AF:

0.00515

AC:

7462

AN:

1448916

Hom.:

160

Cov.:

AF XY:

0.00584

AC XY:

4207

AN XY:

719792

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00196

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0677

Gnomad4 SAS exome

AF:

0.0308

Gnomad4 FIN exome

AF:

0.00143

Gnomad4 NFE exome

AF:

0.00134

Gnomad4 OTH exome

AF:

0.00900

GnomAD4 genome

AF:

0.00527

AC:

800

AN:

151882

Hom.:

Cov.:

AF XY:

0.00592

AC XY:

439

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.00193

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0725

Gnomad4 SAS

AF:

0.0399

Gnomad4 FIN

AF:

0.00274

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.00618

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 27, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 05, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

AUTS2-related disorder

Benign:1

Mar 29, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

7-70790590-GCCACCACCACCACCACCA-GCCACCACCACCACCACCACCACCA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over