NM_017594.5:c.-37+2517T>A

Variant names:

• chr9-90640235-A-T
• rs1331503
• NM_017594.5:c.-37+2517T>A

Variant summary

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

The NM_017594.5(DIRAS2):​c.-37+2517T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,036 control chromosomes in the GnomAD database, including 27,539 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 0.60 (27539 hom., cov: 32)
• Consequence: DIRAS2 NM_017594.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.668 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIRAS2	NM_017594.5	MANE Select	c.-37+2517T>A		intron	N/A	NP_060064.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIRAS2	ENST00000375765.5	TSL:1 MANE Select	c.-37+2517T>A		intron	N/A	ENSP00000364919.3	Q96HU8
	DIRAS2	ENST00000636786.1	TSL:4	c.-155+2517T>A		intron	N/A	ENSP00000490457.1	A0A1B0GVC3
	DIRAS2	ENST00000637905.1	TSL:4	c.-337+2517T>A		intron	N/A	ENSP00000490853.1	A0A1B0GWA9

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90574 AN: 151918 Hom.: 27529 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.596 AC: 90622 AN: 152036 Hom.: 27539 Cov.: 32 AF XY: 0.595 AC XY: 44207 AN XY: 74302

African (AFR) AF: 0.497 AC: 20593 AN: 41438

American (AMR) AF: 0.535 AC: 8171 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2426 AN: 3472

East Asian (EAS) AF: 0.451 AC: 2334 AN: 5170

South Asian (SAS) AF: 0.688 AC: 3319 AN: 4826

European-Finnish (FIN) AF: 0.629 AC: 6640 AN: 10556

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45063 AN: 67980

Other (OTH) AF: 0.629 AC: 1325 AN: 2106

Alfa AF: 0.630 Hom.: 3767

Bravo AF: 0.583

Asia WGS AF: 0.556 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.41
PhyloP100		0.15
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: rs1331503; hg19: chr9-93402517;