rs2297354

Positions:

• chr9-90642058-G-C
• chr9-90642058-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIRAS2	NM_017594.5	c.-37+694C>G		intron_variant		ENST00000375765.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIRAS2	ENST00000375765.5	c.-37+694C>G		intron_variant		1	NM_017594.5	P1
DIRAS2	ENST00000636786.1	c.-155+694C>G		intron_variant		4
DIRAS2	ENST00000637905.1	c.-337+694C>G		intron_variant		4

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

Gnomad4 AFR AF: 0.00217

Gnomad4 AMR AF: 0.0104

Gnomad4 ASJ AF: 0.0207

Gnomad4 EAS AF: 0.0680

Gnomad4 SAS AF: 0.0801

Gnomad4 FIN AF: 0.0501

Gnomad4 NFE AF: 0.0125

Gnomad4 OTH AF: 0.0166

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.4
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs2297354; hg19: chr9-93404340;