7-70790590-GCCACCACCACCACCACCA-GCCACCACCACCACCA

Position:

• chr7-70790590-GCCACCACCACCACCACCA-GCCACCACCACCACCA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_015570.4(AUTS2):​c.3398_3400delACC​(p.His1133del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000724 in 1,597,498 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (0 hom.)
• Consequence: AUTS2 NM_015570.4 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 3.63

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 7-70790590-GCCA-G is Benign according to our data. Variant chr7-70790590-GCCA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1174872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-70790590-GCCA-G is described in Lovd as [Likely_benign]. Variant chr7-70790590-GCCA-G is described in Lovd as [Likely_benign]. Variant chr7-70790590-GCCA-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00134 (203/151884) while in subpopulation EAS AF= 0.00491 (25/5090). AF 95% confidence interval is 0.00341. There are 0 homozygotes in gnomad4. There are 107 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 203 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.3398_3400delACC	p.His1133del	disruptive_inframe_deletion	19/19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.3398_3400delACC	p.His1133del	disruptive_inframe_deletion	19/19	1	NM_015570.4	ENSP00000344087.4

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 205 AN: 151770 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00370

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000918

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00529

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.00474 AC: 900 AN: 189948 Hom.: 0 AF XY: 0.00475 AC XY: 491 AN XY: 103280

Gnomad AFR exome AF: 0.00842

Gnomad AMR exome AF: 0.00285

Gnomad ASJ exome AF: 0.00235

Gnomad EAS exome AF: 0.00986

Gnomad SAS exome AF: 0.00293

Gnomad FIN exome AF: 0.00462

Gnomad NFE exome AF: 0.00494

Gnomad OTH exome AF: 0.00322

GnomAD4 exome AF: 0.000659 AC: 953 AN: 1445614 Hom.: 0 AF XY: 0.000685 AC XY: 492 AN XY: 717972

Gnomad4 AFR exome AF: 0.00410

Gnomad4 AMR exome AF: 0.00176

Gnomad4 ASJ exome AF: 0.000466

Gnomad4 EAS exome AF: 0.00313

Gnomad4 SAS exome AF: 0.000854

Gnomad4 FIN exome AF: 0.00116

Gnomad4 NFE exome AF: 0.000387

Gnomad4 OTH exome AF: 0.000686

GnomAD4 genome AF: 0.00134 AC: 203 AN: 151884 Hom.: 0 Cov.: 32 AF XY: 0.00144 AC XY: 107 AN XY: 74204

Gnomad4 AFR AF: 0.00369

Gnomad4 AMR AF: 0.000916

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00491

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000475

Bravo AF: 0.00118

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2020	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Autism spectrum disorder due to AUTS2 deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 06, 2021

- -

AUTS2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 17, 2021

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

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: rs538005366; hg19: chr7-70255576;