rs2851510

Variant names:

• chr7-69615214-A-G
• rs2851510
• NM_015570.4:c.309+15252A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015570.4(AUTS2):​c.309+15252A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,032 control chromosomes in the GnomAD database, including 29,141 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (29141 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 4 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), G2P, Orphanet
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.309+15252A>G		intron_variant	Intron 1 of 18	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.309+15252A>G		intron_variant	Intron 1 of 18	1	NM_015570.4	ENSP00000344087.4

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93569 AN: 151914 Hom.: 29125 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.616 AC: 93619 AN: 152032 Hom.: 29141 Cov.: 32 AF XY: 0.614 AC XY: 45616 AN XY: 74310

African (AFR) AF: 0.537 AC: 22244 AN: 41436

American (AMR) AF: 0.610 AC: 9318 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2089 AN: 3472

East Asian (EAS) AF: 0.704 AC: 3639 AN: 5170

South Asian (SAS) AF: 0.626 AC: 3018 AN: 4818

European-Finnish (FIN) AF: 0.645 AC: 6808 AN: 10556

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.651 AC: 44278 AN: 67988

Other (OTH) AF: 0.615 AC: 1296 AN: 2106

Alfa AF: 0.625 Hom.: 5192

Bravo AF: 0.611

Asia WGS AF: 0.637 AC: 2215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.69
DANN	Benign	0.59
PhyloP100		-1.1
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: rs2851510; hg19: chr7-69080200;