rs2293501

Positions:

• chr7-70786937-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.2309-272G>A		intron_variant		ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.2309-272G>A		intron_variant		1	NM_015570.4	ENSP00000344087	P4

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

Gnomad4 AFR exome AF: 0.600

Gnomad4 AMR exome AF: 0.647

Gnomad4 ASJ exome AF: 0.616

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.612

Gnomad4 FIN exome AF: 0.789

Gnomad4 NFE exome AF: 0.744

Gnomad4 OTH exome AF: 0.683

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

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.654

Alfa AF: 0.722 Hom.: 52104

Bravo AF: 0.668

Asia WGS AF: 0.533 AC: 1854 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.41
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs2293501; hg19: chr7-70251923;