rs690232

chr9-90620156-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIRAS2	NM_017594.5	c.-36-6293C>T		intron_variant		ENST00000375765.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIRAS2	ENST00000375765.5	c.-36-6293C>T		intron_variant		1	NM_017594.5	P1
DIRAS2	ENST00000636786.1	c.-37+5902C>T		intron_variant		4
DIRAS2	ENST00000637905.1	c.-37+5720C>T		intron_variant		4

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

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.284

Alfa AF: 0.296 Hom.: 13784

Bravo AF: 0.290

Asia WGS AF: 0.383 AC: 1333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.69
Dann	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs690232; hg19: chr9-93382438;