9-90615619-C-T

Variant names:

• chr9-90615619-C-T
• rs1017753
• NM_017594.5:c.-36-1756G>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.-36-1756G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,050 control chromosomes in the GnomAD database, including 19,361 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 0.50 (19361 hom., cov: 32)
• Consequence: DIRAS2 NM_017594.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.512 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.-36-1756G>A		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.-36-1756G>A		intron	N/A	ENSP00000364919.3
	DIRAS2	ENST00000636786.1	TSL:4	c.-36-1756G>A		intron	N/A	ENSP00000490457.1
	DIRAS2	ENST00000637905.1	TSL:4	c.-36-1756G>A		intron	N/A	ENSP00000490853.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76505 AN: 151932 Hom.: 19346 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.504 AC: 76567 AN: 152050 Hom.: 19361 Cov.: 32 AF XY: 0.505 AC XY: 37546 AN XY: 74316

African (AFR) AF: 0.471 AC: 19513 AN: 41460

American (AMR) AF: 0.489 AC: 7474 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2111 AN: 3472

East Asian (EAS) AF: 0.439 AC: 2271 AN: 5170

South Asian (SAS) AF: 0.517 AC: 2490 AN: 4816

European-Finnish (FIN) AF: 0.553 AC: 5840 AN: 10566

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.517 AC: 35122 AN: 67972

Other (OTH) AF: 0.521 AC: 1101 AN: 2114

Alfa AF: 0.510 Hom.: 54267

Bravo AF: 0.499

Asia WGS AF: 0.484 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.28
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1017753; hg19: chr9-93377901;