chr9-90613815-T-G

Position:

• chr9-90613815-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017594.5(DIRAS2):​c.13A>C​(p.Ser5Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DIRAS2 NM_017594.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.84

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIRAS2	NM_017594.5	c.13A>C	p.Ser5Arg	missense_variant	2/2	ENST00000375765.5	NP_060064.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIRAS2	ENST00000375765.5	c.13A>C	p.Ser5Arg	missense_variant	2/2	1	NM_017594.5	ENSP00000364919.3
DIRAS2	ENST00000636786.1	c.13A>C	p.Ser5Arg	missense_variant	3/3	4		ENSP00000490457.1
DIRAS2	ENST00000637905.1	c.13A>C	p.Ser5Arg	missense_variant	3/3	4		ENSP00000490853.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.13A>C (p.S5R) alteration is located in exon 2 (coding exon 1) of the DIRAS2 gene. This alteration results from a A to C substitution at nucleotide position 13, causing the serine (S) at amino acid position 5 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T;T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.54	N;.;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.8	N;.;.
REVEL	Uncertain	0.39
Sift	Benign	0.045	D;.;.
Sift4G	Uncertain	0.051	T;.;.
Polyphen		0.92	P;.;.
Vest4		0.74
MutPred		0.22		Gain of solvent accessibility (P = 0.0365);Gain of solvent accessibility (P = 0.0365);Gain of solvent accessibility (P = 0.0365);
MVP		0.84
MPC		2.2
ClinPred		0.94	D
GERP RS		5.1
Varity_R		0.42
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-93376097;