Variant 7-70790590-GCCACCACCACCACCACCA-GCCACCACCACCACCACCACCACCA details in Genebe, Genetics Data Aggregator

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/exons	MANE	Protein	UniProt
AUTS2	NM_015570.4 linkuse as main transcript	c.3395_3400dupACCACC	p.His1132_His1133dup	disruptive_inframe_insertion	19/19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10 linkuse as main transcript	c.3395_3400dupACCACC	p.His1132_His1133dup	disruptive_inframe_insertion	19/19	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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 27, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 05, 2017	- -

AUTS2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 29, 2019

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.

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