7-69598633-AGCGGCGGCG-AGCGGCGGCGGCGGCG

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_015570.4(AUTS2):​c.-1006_-1001dupGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000538 in 148,804 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 0.000055 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: AUTS2 NM_015570.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000546 (7/128198) while in subpopulation SAS AF= 0.000265 (1/3780). AF 95% confidence interval is 0.0000394. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.-1006_-1001dupGGCGGC		5_prime_UTR_variant	Exon 1 of 19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771	c.-1006_-1001dupGGCGGC		5_prime_UTR_variant	Exon 1 of 19	1	NM_015570.4	ENSP00000344087.4
AUTS2	ENST00000644939	c.-1006_-1001dupGGCGGC		5_prime_UTR_variant	Exon 1 of 19			ENSP00000496726.1

Frequencies

GnomAD3 genomes AF: 0.0000546 AC: 7 AN: 128166 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000242

Gnomad SAS AF: 0.000263

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000169

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000485 AC: 1 AN: 20606 Hom.: 0 Cov.: 0 AF XY: 0.0000761 AC XY: 1 AN XY: 13144

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000756

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000546 AC: 7 AN: 128198 Hom.: 0 Cov.: 30 AF XY: 0.0000798 AC XY: 5 AN XY: 62664

Gnomad4 AFR AF: 0.000118

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000243

Gnomad4 SAS AF: 0.000265

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000169

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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: rs572172462; hg19: chr7-69063619;