NM_017594.5:c.-36-1145A>C

Variant names:

• chr9-90615008-T-G
• rs690111
• NM_017594.5:c.-36-1145A>C

Variant summary

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

The NM_017594.5(DIRAS2):​c.-36-1145A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 152,026 control chromosomes in the GnomAD database, including 35,536 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 0.68 (35536 hom., cov: 32)
• Consequence: DIRAS2 NM_017594.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• Publications: 6 publications found

Genes affected

DIRAS2 (HGNC:19323): (DIRAS family GTPase 2) DIRAS2 belongs to a distinct branch of the functionally diverse Ras (see HRAS; MIM 190020) superfamily of monomeric GTPases.[supplied by OMIM, Apr 2004]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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_017594.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIRAS2	NM_017594.5	MANE Select	c.-36-1145A>C		intron	N/A	NP_060064.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIRAS2	ENST00000375765.5	TSL:1 MANE Select	c.-36-1145A>C		intron	N/A	ENSP00000364919.3
	DIRAS2	ENST00000636786.1	TSL:4	c.-36-1145A>C		intron	N/A	ENSP00000490457.1
	DIRAS2	ENST00000637905.1	TSL:4	c.-36-1145A>C		intron	N/A	ENSP00000490853.1

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102762 AN: 151908 Hom.: 35524 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.676 AC: 102825 AN: 152026 Hom.: 35536 Cov.: 32 AF XY: 0.676 AC XY: 50232 AN XY: 74358

African (AFR) AF: 0.528 AC: 21851 AN: 41412

American (AMR) AF: 0.693 AC: 10581 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2719 AN: 3468

East Asian (EAS) AF: 0.688 AC: 3565 AN: 5182

South Asian (SAS) AF: 0.603 AC: 2904 AN: 4814

European-Finnish (FIN) AF: 0.751 AC: 7941 AN: 10580

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50836 AN: 67980

Other (OTH) AF: 0.685 AC: 1446 AN: 2112

Alfa AF: 0.725 Hom.: 64247

Bravo AF: 0.669

Asia WGS AF: 0.656 AC: 2286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.49
PhyloP100		-2.7
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: rs690111; hg19: chr9-93377290;