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

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_015570.4(AUTS2):c.3398_3400dupACC(p.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 0.00816 in 1,600,800 control chromosomes in the GnomAD database, including 75 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0062 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 72 hom. )

Consequence

AUTS2
NM_015570.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

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 -9 ACMG points.

BP6

Variant 7-70790590-G-GCCA is Benign according to our data. Variant chr7-70790590-G-GCCA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 374065.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2, Benign=2}.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00624 (947/151882) while in subpopulation SAS AF= 0.0265 (126/4762). AF 95% confidence interval is 0.0227. There are 3 homozygotes in gnomad4. There are 459 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 947 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUTS2	NM_015570.4 linkuse as main transcript	c.3398_3400dupACC	p.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.3398_3400dupACC	p.His1133dup	disruptive_inframe_insertion	19/19	1	NM_015570.4	ENSP00000344087.4		Q8WXX7-1

Frequencies

GnomAD3 genomes

AF:

0.00624

AC:

947

AN:

151768

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.00728

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.000980

Gnomad SAS

AF:

0.0266

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00785

Gnomad OTH

AF:

0.00720

GnomAD3 exomes

AF:

0.00898

AC:

1706

AN:

189948

Hom.:

AF XY:

0.0105

AC XY:

1085

AN XY:

103280

show subpopulations

Gnomad AFR exome

AF:

0.00230

Gnomad AMR exome

AF:

0.00628

Gnomad ASJ exome

AF:

0.00858

Gnomad EAS exome

AF:

0.00135

Gnomad SAS exome

AF:

0.0276

Gnomad FIN exome

AF:

0.00228

Gnomad NFE exome

AF:

0.00775

Gnomad OTH exome

AF:

0.00864

GnomAD4 exome

AF:

0.00836

AC:

12111

AN:

1448918

Hom.:

Cov.:

AF XY:

0.00899

AC XY:

6471

AN XY:

719784

show subpopulations

Gnomad4 AFR exome

AF:

0.00244

Gnomad4 AMR exome

AF:

0.00577

Gnomad4 ASJ exome

AF:

0.00747

Gnomad4 EAS exome

AF:

0.00137

Gnomad4 SAS exome

AF:

0.0259

Gnomad4 FIN exome

AF:

0.00215

Gnomad4 NFE exome

AF:

0.00772

Gnomad4 OTH exome

AF:

0.00912

GnomAD4 genome

AF:

0.00624

AC:

947

AN:

151882

Hom.:

Cov.:

AF XY:

0.00619

AC XY:

459

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.00251

Gnomad4 AMR

AF:

0.00727

Gnomad4 ASJ

AF:

0.00606

Gnomad4 EAS

AF:

0.000982

Gnomad4 SAS

AF:

0.0265

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00785

Gnomad4 OTH

AF:

0.00760

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 11, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Oct 27, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

Autism spectrum disorder due to AUTS2 deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Jan 01, 2016

This variant was classified as: Uncertain significance. -

Autism;C0557874:Global developmental delay

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Mar 31, 2015

- -

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