NM_017594.5:c.*2232G>C

Variant names:

• chr9-90610996-C-G
• rs16906711
• NM_017594.5:c.*2232G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017594.5(DIRAS2):​c.*2232G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 152,154 control chromosomes in the GnomAD database, including 963 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 0.087 (963 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DIRAS2 NM_017594.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIRAS2	NM_017594.5	c.*2232G>C		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.*2232G>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_017594.5	ENSP00000364919.3

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13202 AN: 152036 Hom.: 952 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0796

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.0845

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.0693

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0781

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0871 AC: 13245 AN: 152154 Hom.: 963 Cov.: 32 AF XY: 0.0876 AC XY: 6518 AN XY: 74388

African (AFR) AF: 0.200 AC: 8298 AN: 41480

American (AMR) AF: 0.0795 AC: 1215 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0375 AC: 130 AN: 3470

East Asian (EAS) AF: 0.0845 AC: 437 AN: 5172

South Asian (SAS) AF: 0.0694 AC: 334 AN: 4816

European-Finnish (FIN) AF: 0.0693 AC: 734 AN: 10586

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0279 AC: 1897 AN: 68024

Other (OTH) AF: 0.0797 AC: 168 AN: 2108

Alfa AF: 0.0598 Hom.: 57

Bravo AF: 0.0934

Asia WGS AF: 0.110 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.067
DANN	Benign	0.40
PhyloP100		-2.1
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: rs16906711; hg19: chr9-93373278;