7-69599743-GGGGGCCGGCGCGGCCGGCGGCGGC-G

Variant names:

• chr7-69599743-GGGGGCCGGCGCGGCCGGCGGCGGC-G
• NM_015570.4:c.96_119delCGGCGCGGCCGGCGGCGGCGGGGC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015570.4(AUTS2):​c.96_119delCGGCGCGGCCGGCGGCGGCGGGGC​(p.Gly33_Ala40del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,198,688 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000025 (1 hom.)
• Consequence: AUTS2 NM_015570.4 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.96_119delCGGCGCGGCCGGCGGCGGCGGGGC	p.Gly33_Ala40del	disruptive_inframe_deletion	Exon 1 of 19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.96_119delCGGCGCGGCCGGCGGCGGCGGGGC	p.Gly33_Ala40del	disruptive_inframe_deletion	Exon 1 of 19	1	NM_015570.4	ENSP00000344087.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000250 AC: 3 AN: 1198688 Hom.: 1 AF XY: 0.00000343 AC XY: 2 AN XY: 582498

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 23776

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 10192

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 16006

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 27248

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 43260

Gnomad4 FIN exome AF: 0.0000524 AC: 2 AN: 38148

Gnomad4 NFE exome AF: 0.00000101 AC: 1 AN: 988028

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 48662

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jul 27, 2022

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 8 amino acids in a non-repeat region; In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-69064729;