chr7-70616753-GTT-G

Variant names:

• chr7-70616753-GTT-G
• rs67691820
• NM_015570.4:c.691-81799_691-81798delTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_015570.4(AUTS2):​c.691-81799_691-81798delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0015 (0 hom., cov: 0)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00146 (191/131246) while in subpopulation AFR AF = 0.00496 (175/35252). AF 95% confidence interval is 0.00436. There are 0 homozygotes in GnomAd4. There are 104 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 191 AD gene.

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.691-81799_691-81798delTT		intron	N/A	NP_056385.1	Q8WXX7-1
	AUTS2	NM_001127231.3		c.691-81799_691-81798delTT		intron	N/A	NP_001120703.1	Q8WXX7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.691-81815_691-81814delTT		intron	N/A	ENSP00000344087.4	Q8WXX7-1
	AUTS2	ENST00000406775.6	TSL:1	c.691-81815_691-81814delTT		intron	N/A	ENSP00000385263.2	Q8WXX7-2
	AUTS2	ENST00000644939.1		c.691-81815_691-81814delTT		intron	N/A	ENSP00000496726.1	A0A2R8Y8C6

Frequencies

GnomAD3 genomes AF: 0.00146 AC: 191 AN: 131264 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00497

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000472

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000991

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000478

Gnomad OTH AF: 0.000569

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00146 AC: 191 AN: 131246 Hom.: 0 Cov.: 0 AF XY: 0.00167 AC XY: 104 AN XY: 62232

African (AFR) AF: 0.00496 AC: 175 AN: 35252

American (AMR) AF: 0.000471 AC: 6 AN: 12730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3296

East Asian (EAS) AF: 0.00 AC: 0 AN: 4370

South Asian (SAS) AF: 0.00 AC: 0 AN: 3930

European-Finnish (FIN) AF: 0.000991 AC: 6 AN: 6056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 210

European-Non Finnish (NFE) AF: 0.0000478 AC: 3 AN: 62780

Other (OTH) AF: 0.000566 AC: 1 AN: 1766

Alfa AF: 0.00 Hom.: 331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs67691820; hg19: chr7-70081739;