chr9-90610767-G-A

Variant names:

• chr9-90610767-G-A
• rs1542479
• NM_017594.5:c.*2461C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-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 rank	MANE	Protein	UniProt
DIRAS2	NM_017594.5	c.*2461C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000375765.5	NP_060064.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIRAS2	ENST00000375765.5	c.*2461C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_017594.5	ENSP00000364919.3

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

African (AFR) AF: 0.00694 AC: 22 AN: 3168

American (AMR) AF: 0.0293 AC: 73 AN: 2492

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 97 AN: 3914

East Asian (EAS) AF: 0.123 AC: 922 AN: 7498

South Asian (SAS) AF: 0.141 AC: 100 AN: 710

European-Finnish (FIN) AF: 0.0593 AC: 166 AN: 2798

Middle Eastern (MID) AF: 0.0415 AC: 18 AN: 434

European-Non Finnish (NFE) AF: 0.0357 AC: 1899 AN: 53212

Other (OTH) AF: 0.0349 AC: 201 AN: 5756

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

African (AFR) AF: 0.00656 AC: 272 AN: 41490

American (AMR) AF: 0.0258 AC: 393 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0309 AC: 107 AN: 3468

East Asian (EAS) AF: 0.0759 AC: 392 AN: 5166

South Asian (SAS) AF: 0.136 AC: 654 AN: 4816

European-Finnish (FIN) AF: 0.0658 AC: 694 AN: 10542

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0354 AC: 2410 AN: 67998

Other (OTH) AF: 0.0423 AC: 89 AN: 2106

Alfa AF: 0.0346 Hom.: 163

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
PhyloP100		0.90
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1542479; hg19: chr9-93373049;