7-70790590-GCCACCACCACCACCACCA-GCCACCA

Variant names:

• chr7-70790590-GCCACCACCACCA-G
• rs538005366
• NM_015570.4:c.3389_3400delACCACCACCACC

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The ENST00000342771.10(AUTS2):​c.3389_3400delACCACCACCACC​(p.His1130_His1133del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000116 in 1,600,724 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: AUTS2 ENST00000342771.10 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.22
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• autism spectrum disorder due to AUTS2 deficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000342771.10
• BP6: Variant 7-70790590-GCCACCACCACCA-G is Benign according to our data. Variant chr7-70790590-GCCACCACCACCA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2012664.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000593 (9/151772) while in subpopulation SAS AF = 0.00021 (1/4768). AF 95% confidence interval is 0.0000197. There are 0 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000342771.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	NM_015570.4	MANE Select	c.3389_3400delACCACCACCACC	p.His1130_His1133del	disruptive_inframe_deletion	Exon 19 of 19	NP_056385.1
	AUTS2	NM_001127231.3		c.3317_3328delACCACCACCACC	p.His1106_His1109del	disruptive_inframe_deletion	Exon 18 of 18	NP_001120703.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.3389_3400delACCACCACCACC	p.His1130_His1133del	disruptive_inframe_deletion	Exon 19 of 19	ENSP00000344087.4
	AUTS2	ENST00000406775.6	TSL:1	c.3317_3328delACCACCACCACC	p.His1106_His1109del	disruptive_inframe_deletion	Exon 18 of 18	ENSP00000385263.2
	AUTS2	ENST00000644939.1		c.3386_3397delACCACCACCACC	p.His1129_His1132del	disruptive_inframe_deletion	Exon 19 of 19	ENSP00000496726.1

Frequencies

GnomAD3 genomes AF: 0.0000593 AC: 9 AN: 151772 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000737 AC: 14 AN: 189948 AF XY: 0.0000871

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000343

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000195

Gnomad NFE exome AF: 0.000111

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000121 AC: 176 AN: 1448952 Hom.: 0 AF XY: 0.000114 AC XY: 82 AN XY: 719806

African (AFR) AF: 0.0000602 AC: 2 AN: 33204

American (AMR) AF: 0.0000467 AC: 2 AN: 42814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25848

East Asian (EAS) AF: 0.00 AC: 0 AN: 38740

South Asian (SAS) AF: 0.0000473 AC: 4 AN: 84616

European-Finnish (FIN) AF: 0.0000391 AC: 2 AN: 51154

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5748

European-Non Finnish (NFE) AF: 0.000146 AC: 162 AN: 1106936

Other (OTH) AF: 0.0000501 AC: 3 AN: 59892

GnomAD4 genome AF: 0.0000593 AC: 9 AN: 151772 Hom.: 0 Cov.: 32 AF XY: 0.0000675 AC XY: 5 AN XY: 74082

African (AFR) AF: 0.0000725 AC: 3 AN: 41354

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4768

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67922

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.0000367 Hom.: 0

Bravo AF: 0.0000491

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.2
Mutation Taster		=100/100

Splicing

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

Other links and lift over

dbSNP: rs538005366; hg19: chr7-70255576;