rs1331503

Positions:

• chr9-90640235-A-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+2517T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,036 control chromosomes in the GnomAD database, including 27,539 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 0.60 (27539 hom., cov: 32)
• Consequence: DIRAS2 NM_017594.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIRAS2	NM_017594.5	c.-37+2517T>A		intron_variant		ENST00000375765.5	NP_060064.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIRAS2	ENST00000375765.5	c.-37+2517T>A		intron_variant		1	NM_017594.5	ENSP00000364919	P1
DIRAS2	ENST00000636786.1	c.-155+2517T>A		intron_variant		4		ENSP00000490457
DIRAS2	ENST00000637905.1	c.-337+2517T>A		intron_variant		4		ENSP00000490853

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90574 AN: 151918 Hom.: 27529 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.596 AC: 90622 AN: 152036 Hom.: 27539 Cov.: 32 AF XY: 0.595 AC XY: 44207 AN XY: 74302

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.629

Alfa AF: 0.630 Hom.: 3767

Bravo AF: 0.583

Asia WGS AF: 0.556 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.41

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: rs1331503; hg19: chr9-93402517;