rs1542479

Positions:

• chr9-90610767-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.*2461C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 232,032 control chromosomes in the GnomAD database, including 274 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 0.033 (150 hom., cov: 32)
  • Exomes 𝑓: 0.044 (124 hom.)
• Consequence: DIRAS2 NM_017594.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904

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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIRAS2	NM_017594.5	c.*2461C>T		3_prime_UTR_variant	2/2	ENST00000375765.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIRAS2	ENST00000375765.5	c.*2461C>T		3_prime_UTR_variant	2/2	1	NM_017594.5	P1

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 5026 AN: 151932 Hom.: 148 Cov.: 32

Gnomad AFR AF: 0.00655

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.0755

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0658

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0427

GnomAD4 exome AF: 0.0437 AC: 3498 AN: 79982 Hom.: 124 Cov.: 0 AF XY: 0.0445 AC XY: 1782 AN XY: 40048

Gnomad4 AFR exome AF: 0.00694

Gnomad4 AMR exome AF: 0.0293

Gnomad4 ASJ exome AF: 0.0248

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.0593

Gnomad4 NFE exome AF: 0.0357

Gnomad4 OTH exome AF: 0.0349

GnomAD4 genome AF: 0.0331 AC: 5032 AN: 152050 Hom.: 150 Cov.: 32 AF XY: 0.0364 AC XY: 2703 AN XY: 74294

Gnomad4 AFR AF: 0.00656

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.0309

Gnomad4 EAS AF: 0.0759

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0658

Gnomad4 NFE AF: 0.0354

Gnomad4 OTH AF: 0.0423

Alfa AF: 0.0363 Hom.: 142

Bravo AF: 0.0270

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.1
DANN	Benign	0.33

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: rs1542479; hg19: chr9-93373049;