NM_017594.5:c.-36-6293C>T

Variant names:

• chr9-90620156-G-A
• rs690232
• NM_017594.5:c.-36-6293C>T

Variant summary

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

The NM_017594.5(DIRAS2):​c.-36-6293C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,010 control chromosomes in the GnomAD database, including 6,560 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 0.29 (6560 hom., cov: 32)
• Consequence: DIRAS2 NM_017594.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 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.-36-6293C>T		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.-36-6293C>T		intron	N/A	ENSP00000364919.3
	DIRAS2	ENST00000636786.1	TSL:4	c.-37+5902C>T		intron	N/A	ENSP00000490457.1
	DIRAS2	ENST00000637905.1	TSL:4	c.-37+5720C>T		intron	N/A	ENSP00000490853.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44476 AN: 151890 Hom.: 6547 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.293 AC: 44526 AN: 152010 Hom.: 6560 Cov.: 32 AF XY: 0.294 AC XY: 21869 AN XY: 74288

African (AFR) AF: 0.264 AC: 10943 AN: 41462

American (AMR) AF: 0.309 AC: 4721 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 841 AN: 3464

East Asian (EAS) AF: 0.426 AC: 2203 AN: 5172

South Asian (SAS) AF: 0.277 AC: 1333 AN: 4806

European-Finnish (FIN) AF: 0.334 AC: 3518 AN: 10540

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19980 AN: 67978

Other (OTH) AF: 0.284 AC: 597 AN: 2104

Alfa AF: 0.295 Hom.: 26195

Bravo AF: 0.290

Asia WGS AF: 0.383 AC: 1333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.69
DANN	Benign	0.47
PhyloP100		-0.64
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: rs690232; hg19: chr9-93382438;