7-70616753-GTTTTTT-GTTTTTTT

Variant names:

• chr7-70616753-G-GT
• rs67691820
• NM_015570.4:c.691-81798dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_015570.4(AUTS2):​c.691-81798dupT 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 0.32 (7322 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.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

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.691-81798dupT		intron	N/A	NP_056385.1	Q8WXX7-1
	AUTS2	NM_001127231.3		c.691-81798dupT		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.691-81816_691-81815insT		intron	N/A	ENSP00000344087.4	Q8WXX7-1
	AUTS2	ENST00000406775.6	TSL:1	c.691-81816_691-81815insT		intron	N/A	ENSP00000385263.2	Q8WXX7-2
	AUTS2	ENST00000644939.1		c.691-81816_691-81815insT		intron	N/A	ENSP00000496726.1	A0A2R8Y8C6

Frequencies

GnomAD3 genomes AF: 0.324 AC: 42570 AN: 131228 Hom.: 7328 Cov.: 0

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.00753

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.324 AC: 42553 AN: 131210 Hom.: 7322 Cov.: 0 AF XY: 0.318 AC XY: 19804 AN XY: 62216

African (AFR) AF: 0.300 AC: 10570 AN: 35232

American (AMR) AF: 0.241 AC: 3068 AN: 12736

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1408 AN: 3288

East Asian (EAS) AF: 0.00755 AC: 33 AN: 4370

South Asian (SAS) AF: 0.235 AC: 925 AN: 3928

European-Finnish (FIN) AF: 0.373 AC: 2269 AN: 6088

Middle Eastern (MID) AF: 0.290 AC: 61 AN: 210

European-Non Finnish (NFE) AF: 0.371 AC: 23277 AN: 62734

Other (OTH) AF: 0.314 AC: 555 AN: 1770

Alfa AF: 0.210 Hom.: 331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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;