7-69598633-AGCGGCGGCG-AGCG

Variant names:

• chr7-69598633-AGCGGCG-A
• rs572172462
• NM_015570.4:c.-1006_-1001delGGCGGC

Variant summary

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

The NM_015570.4(AUTS2):​c.-1006_-1001delGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000336 in 148,750 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000016 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: AUTS2 NM_015570.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02
• Publications: 0 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), Orphanet, G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

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

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	NM_015570.4	MANE Select	c.-1006_-1001delGGCGGC		5_prime_UTR	Exon 1 of 19	NP_056385.1	Q8WXX7-1
	AUTS2	NM_001127231.3		c.-1006_-1001delGGCGGC		5_prime_UTR	Exon 1 of 18	NP_001120703.1	Q8WXX7-2
	AUTS2	NM_001127232.3		c.-1006_-1001delGGCGGC		5_prime_UTR	Exon 1 of 5	NP_001120704.1	Q8WXX7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.-1006_-1001delGGCGGC		5_prime_UTR	Exon 1 of 19	ENSP00000344087.4	Q8WXX7-1
	AUTS2	ENST00000644939.1		c.-1006_-1001delGGCGGC		5_prime_UTR	Exon 1 of 19	ENSP00000496726.1	A0A2R8Y8C6

Frequencies

GnomAD3 genomes AF: 0.0000156 AC: 2 AN: 128166 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000752

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000169

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000146 AC: 3 AN: 20584 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 13126

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 144

American (AMR) AF: 0.00 AC: 0 AN: 140

Ashkenazi Jewish (ASJ) AF: 0.00410 AC: 1 AN: 244

East Asian (EAS) AF: 0.00 AC: 0 AN: 302

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 64

European-Non Finnish (NFE) AF: 0.0000757 AC: 1 AN: 13218

Other (OTH) AF: 0.00 AC: 0 AN: 874

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000156 AC: 2 AN: 128166 Hom.: 0 Cov.: 30 AF XY: 0.0000160 AC XY: 1 AN XY: 62616

African (AFR) AF: 0.00 AC: 0 AN: 33898

American (AMR) AF: 0.0000752 AC: 1 AN: 13300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3110

East Asian (EAS) AF: 0.00 AC: 0 AN: 4138

South Asian (SAS) AF: 0.00 AC: 0 AN: 3800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 166

European-Non Finnish (NFE) AF: 0.0000169 AC: 1 AN: 59246

Other (OTH) AF: 0.00 AC: 0 AN: 1742

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

Splicing

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

Other links and lift over

dbSNP: rs572172462; hg19: chr7-69063619;