7-69599717-C-A

Variant names:

• chr7-69599717-C-A
• rs1263138285
• NM_015570.4:c.64C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015570.4(AUTS2):​c.64C>A​(p.Arg22Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000852 in 1,173,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: AUTS2 NM_015570.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP7: Synonymous conserved (PhyloP=1.82 with no splicing effect.

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.64C>A	p.Arg22Arg	synonymous	Exon 1 of 19	NP_056385.1	Q8WXX7-1
	AUTS2	NM_001127231.3		c.64C>A	p.Arg22Arg	synonymous	Exon 1 of 18	NP_001120703.1	Q8WXX7-2
	AUTS2	NM_001127232.3		c.64C>A	p.Arg22Arg	synonymous	Exon 1 of 5	NP_001120704.1	Q8WXX7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.64C>A	p.Arg22Arg	synonymous	Exon 1 of 19	ENSP00000344087.4	Q8WXX7-1
	AUTS2	ENST00000406775.6	TSL:1	c.64C>A	p.Arg22Arg	synonymous	Exon 1 of 18	ENSP00000385263.2	Q8WXX7-2
	AUTS2	ENST00000403018.3	TSL:1	c.64C>A	p.Arg22Arg	synonymous	Exon 1 of 5	ENSP00000385572.2	Q8WXX7-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.52e-7 AC: 1 AN: 1173092 Hom.: 0 Cov.: 32 AF XY: 0.00000176 AC XY: 1 AN XY: 567314

African (AFR) AF: 0.00 AC: 0 AN: 23316

American (AMR) AF: 0.00 AC: 0 AN: 9118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15536

East Asian (EAS) AF: 0.00 AC: 0 AN: 27156

South Asian (SAS) AF: 0.00 AC: 0 AN: 36056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3208

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 974930

Other (OTH) AF: 0.00 AC: 0 AN: 47604

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	16
DANN	Benign	0.96
PhyloP100		1.8
PromoterAI		-0.025	Neutral

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: rs1263138285; hg19: chr7-69064703;