7-70790590-GCCACCACCACCACCACCA-GCCACCACCA

Variant names:

• chr7-70790590-GCCACCACCA-G
• rs538005366
• NM_015570.4:c.3392_3400delACCACCACC

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The NM_015570.4(AUTS2):​c.3392_3400delACCACCACC​(p.His1131_His1133del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000284 in 1,600,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: AUTS2 NM_015570.4 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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 -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_015570.4
• BP6: Variant 7-70790590-GCCACCACCA-G is Benign according to our data. Variant chr7-70790590-GCCACCACCA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 787554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000303 (46/151886) while in subpopulation AFR AF = 0.000289 (12/41476). AF 95% confidence interval is 0.000167. There are 0 homozygotes in GnomAd4. There are 25 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 46 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015570.4. 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.3392_3400delACCACCACC	p.His1131_His1133del	disruptive_inframe_deletion	Exon 19 of 19	NP_056385.1
	AUTS2	NM_001127231.3		c.3320_3328delACCACCACC	p.His1107_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.3392_3400delACCACCACC	p.His1131_His1133del	disruptive_inframe_deletion	Exon 19 of 19	ENSP00000344087.4
	AUTS2	ENST00000406775.6	TSL:1	c.3320_3328delACCACCACC	p.His1107_His1109del	disruptive_inframe_deletion	Exon 18 of 18	ENSP00000385263.2
	AUTS2	ENST00000644939.1		c.3389_3397delACCACCACC	p.His1130_His1132del	disruptive_inframe_deletion	Exon 19 of 19	ENSP00000496726.1

Frequencies

GnomAD3 genomes AF: 0.000303 AC: 46 AN: 151772 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000363 AC: 69 AN: 189948 AF XY: 0.000407

Gnomad AFR exome AF: 0.000177

Gnomad AMR exome AF: 0.000103

Gnomad ASJ exome AF: 0.00259

Gnomad EAS exome AF: 0.000426

Gnomad FIN exome AF: 0.000195

Gnomad NFE exome AF: 0.000234

Gnomad OTH exome AF: 0.00121

GnomAD4 exome AF: 0.000282 AC: 408 AN: 1448954 Hom.: 0 AF XY: 0.000295 AC XY: 212 AN XY: 719808

African (AFR) AF: 0.000542 AC: 18 AN: 33204

American (AMR) AF: 0.000234 AC: 10 AN: 42814

Ashkenazi Jewish (ASJ) AF: 0.00290 AC: 75 AN: 25848

East Asian (EAS) AF: 0.000258 AC: 10 AN: 38740

South Asian (SAS) AF: 0.000177 AC: 15 AN: 84616

European-Finnish (FIN) AF: 0.000176 AC: 9 AN: 51154

Middle Eastern (MID) AF: 0.000870 AC: 5 AN: 5748

European-Non Finnish (NFE) AF: 0.000222 AC: 246 AN: 1106938

Other (OTH) AF: 0.000334 AC: 20 AN: 59892

GnomAD4 genome AF: 0.000303 AC: 46 AN: 151886 Hom.: 0 Cov.: 32 AF XY: 0.000337 AC XY: 25 AN XY: 74206

African (AFR) AF: 0.000289 AC: 12 AN: 41476

American (AMR) AF: 0.000196 AC: 3 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3466

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5090

South Asian (SAS) AF: 0.00 AC: 0 AN: 4762

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67914

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.000257 Hom.: 0

Bravo AF: 0.000359

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.2
Mutation Taster		=110/90	polymorphism

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; COSMIC: COSV108167787; COSMIC: COSV108167787;