chr7-69599703-G-A

Variant names:

• chr7-69599703-G-A
• NM_015570.4:c.50G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015570.4(AUTS2):​c.50G>A​(p.Arg17Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000171 in 1,172,992 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: 0.0000017 (0 hom.)
• Consequence: AUTS2 NM_015570.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.00

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39977247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.50G>A	p.Arg17Gln	missense_variant	Exon 1 of 19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.50G>A	p.Arg17Gln	missense_variant	Exon 1 of 19	1	NM_015570.4	ENSP00000344087.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000171 AC: 2 AN: 1172992 Hom.: 0 Cov.: 32 AF XY: 0.00000353 AC XY: 2 AN XY: 567130

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000205

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	.;.;T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Pathogenic	0.85	D
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.1	.;L;L;L
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-0.86	.;N;N;N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	.;D;D;D
Sift4G	Pathogenic	0.0	.;D;D;D
Polyphen		0.94	.;P;P;.
Vest4		0.24, 0.24, 0.30
MutPred		0.36		Gain of methylation at K13 (P = 0.1704);Gain of methylation at K13 (P = 0.1704);Gain of methylation at K13 (P = 0.1704);Gain of methylation at K13 (P = 0.1704);
MVP		0.61
MPC		2.3
ClinPred		0.91	D
GERP RS		3.7
Varity_R		0.24
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-69064689;