9-90642058-G-C

Variant names:

• chr9-90642058-G-C
• rs2297354
• NM_017594.5:c.-37+694C>G

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+694C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 152,308 control chromosomes in the GnomAD database, including 56 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 0.016 (56 hom., cov: 33)
• Consequence: DIRAS2 NM_017594.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 1 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]

ENSG00000302391 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0735 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.-37+694C>G		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.-37+694C>G		intron	N/A	ENSP00000364919.3
	DIRAS2	ENST00000636786.1	TSL:4	c.-155+694C>G		intron	N/A	ENSP00000490457.1
	DIRAS2	ENST00000637905.1	TSL:4	c.-337+694C>G		intron	N/A	ENSP00000490853.1

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2480 AN: 152190 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.0677

Gnomad SAS AF: 0.0792

Gnomad FIN AF: 0.0501

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.0167

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

GnomAD4 genome AF: 0.0163 AC: 2485 AN: 152308 Hom.: 56 Cov.: 33 AF XY: 0.0191 AC XY: 1425 AN XY: 74480

African (AFR) AF: 0.00217 AC: 90 AN: 41564

American (AMR) AF: 0.0104 AC: 159 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3472

East Asian (EAS) AF: 0.0680 AC: 352 AN: 5174

South Asian (SAS) AF: 0.0801 AC: 387 AN: 4832

European-Finnish (FIN) AF: 0.0501 AC: 532 AN: 10622

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0125 AC: 853 AN: 68018

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.00473 Hom.: 0

Bravo AF: 0.0115

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.4
DANN	Benign	0.69
PhyloP100		-0.029
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: rs2297354; hg19: chr9-93404340;