7-70786937-G-A

Variant names:

• chr7-70786937-G-A
• rs2293501
• NM_015570.4:c.2309-272G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015570.4(AUTS2):​c.2309-272G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 520,948 control chromosomes in the GnomAD database, including 126,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (35562 hom., cov: 30)
  • Exomes 𝑓: 0.70 (91201 hom.)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.492
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-70786937-G-A is Benign according to our data. Variant chr7-70786937-G-A is described in ClinVar as Benign. ClinVar VariationId is 1222220.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.742 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.2309-272G>A		intron	N/A	NP_056385.1	Q8WXX7-1
	AUTS2	NM_001127231.3		c.2237-272G>A		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.2309-272G>A		intron	N/A	ENSP00000344087.4	Q8WXX7-1
	AUTS2	ENST00000406775.6	TSL:1	c.2237-272G>A		intron	N/A	ENSP00000385263.2	Q8WXX7-2
	AUTS2	ENST00000644939.1		c.2306-272G>A		intron	N/A	ENSP00000496726.1	A0A2R8Y8C6

Frequencies

GnomAD3 genomes AF: 0.679 AC: 102966 AN: 151674 Hom.: 35541 Cov.: 30

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.651

GnomAD4 exome AF: 0.695 AC: 256587 AN: 369156 Hom.: 91201 Cov.: 2 AF XY: 0.690 AC XY: 137385 AN XY: 199012

African (AFR) AF: 0.600 AC: 6423 AN: 10706

American (AMR) AF: 0.647 AC: 10305 AN: 15930

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 6683 AN: 10842

East Asian (EAS) AF: 0.429 AC: 9843 AN: 22920

South Asian (SAS) AF: 0.612 AC: 26953 AN: 44016

European-Finnish (FIN) AF: 0.789 AC: 15094 AN: 19136

Middle Eastern (MID) AF: 0.636 AC: 972 AN: 1528

European-Non Finnish (NFE) AF: 0.744 AC: 165963 AN: 223074

Other (OTH) AF: 0.683 AC: 14351 AN: 21004

GnomAD4 genome AF: 0.679 AC: 103036 AN: 151792 Hom.: 35562 Cov.: 30 AF XY: 0.676 AC XY: 50115 AN XY: 74176

African (AFR) AF: 0.599 AC: 24757 AN: 41326

American (AMR) AF: 0.641 AC: 9788 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2122 AN: 3468

East Asian (EAS) AF: 0.432 AC: 2219 AN: 5138

South Asian (SAS) AF: 0.598 AC: 2859 AN: 4784

European-Finnish (FIN) AF: 0.791 AC: 8331 AN: 10534

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50825 AN: 67960

Other (OTH) AF: 0.654 AC: 1383 AN: 2114

Alfa AF: 0.714 Hom.: 71499

Bravo AF: 0.668

Asia WGS AF: 0.533 AC: 1854 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.41
DANN	Benign	0.33
PhyloP100		-0.49
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: rs2293501; hg19: chr7-70251923;