7-69598633-AGCGGCGGCG-AGCGGCG

Variant names:

• chr7-69598633-AGCG-A
• rs572172462
• NM_015570.4:c.-1003_-1001delGGC

Variant summary

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

The NM_015570.4(AUTS2):​c.-1003_-1001delGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 148,204 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. 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: 0.013 (0 hom.)
• Consequence: AUTS2 NM_015570.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• 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 0 ACMG points.

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.-1003_-1001delGGC		5_prime_UTR	Exon 1 of 19	NP_056385.1	Q8WXX7-1
	AUTS2	NM_001127231.3		c.-1003_-1001delGGC		5_prime_UTR	Exon 1 of 18	NP_001120703.1	Q8WXX7-2
	AUTS2	NM_001127232.3		c.-1003_-1001delGGC		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.-1003_-1001delGGC		5_prime_UTR	Exon 1 of 19	ENSP00000344087.4	Q8WXX7-1
	AUTS2	ENST00000644939.1		c.-1003_-1001delGGC		5_prime_UTR	Exon 1 of 19	ENSP00000496726.1	A0A2R8Y8C6

Frequencies

GnomAD3 genomes AF: 0.0000156 AC: 2 AN: 128138 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000338

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0130 AC: 260 AN: 20066 Hom.: 0 AF XY: 0.0130 AC XY: 166 AN XY: 12770

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

African (AFR) AF: 0.0214 AC: 3 AN: 140

American (AMR) AF: 0.00735 AC: 1 AN: 136

Ashkenazi Jewish (ASJ) AF: 0.00420 AC: 1 AN: 238

East Asian (EAS) AF: 0.0175 AC: 5 AN: 286

South Asian (SAS) AF: 0.0124 AC: 58 AN: 4660

European-Finnish (FIN) AF: 0.0123 AC: 10 AN: 812

Middle Eastern (MID) AF: 0.0172 AC: 1 AN: 58

European-Non Finnish (NFE) AF: 0.0133 AC: 171 AN: 12886

Other (OTH) AF: 0.0118 AC: 10 AN: 850

⚠️ 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: 128138 Hom.: 0 Cov.: 30 AF XY: 0.0000319 AC XY: 2 AN XY: 62602

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

African (AFR) AF: 0.00 AC: 0 AN: 33896

American (AMR) AF: 0.00 AC: 0 AN: 13298

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: 7994

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

European-Non Finnish (NFE) AF: 0.0000338 AC: 2 AN: 59240

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

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;