chr7-70790590-GCCACCACCACCA-G

Position:

• chr7-70790590-GCCACCACCACCA-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_015570.4(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. 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 NM_015570.4 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.22

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 Likely_benign. Variant got -6 ACMG points.

• 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 id is 2012664.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.3389_3400delACCACCACCACC	p.His1130_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.3389_3400delACCACCACCACC	p.His1130_His1133del	disruptive_inframe_deletion	19/19	1	NM_015570.4	ENSP00000344087.4

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

GnomAD3 exomes AF: 0.0000737 AC: 14 AN: 189948 Hom.: 0 AF XY: 0.0000871 AC XY: 9 AN XY: 103280

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 SAS exome AF: 0.0000396

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

Gnomad4 AFR exome AF: 0.0000602

Gnomad4 AMR exome AF: 0.0000467

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000473

Gnomad4 FIN exome AF: 0.0000391

Gnomad4 NFE exome AF: 0.000146

Gnomad4 OTH exome AF: 0.0000501

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

Gnomad4 AFR AF: 0.0000725

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.0000589

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000491

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 27, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

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;