3-49026415-G-T

Variant names:

• chr3-49026415-G-T
• NM_000884.3:c.915C>A
• IMPDH2 p.Val305Val

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP7

The NM_000884.3(IMPDH2):​c.915C>A​(p.Val305Val) variant causes a synonymous change involving the alteration of a non-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. Synonymous variant affecting the same amino acid position (i.e. V305V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IMPDH2 NM_000884.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10
• Publications: 0 publications found

Genes affected

IMPDH2 (HGNC:6053): (inosine monophosphate dehydrogenase 2) This gene encodes the rate-limiting enzyme in the de novo guanine nucleotide biosynthesis. It is thus involved in maintaining cellular guanine deoxy- and ribonucleotide pools needed for DNA and RNA synthesis. The encoded protein catalyzes the NAD-dependent oxidation of inosine-5'-monophosphate into xanthine-5'-monophosphate, which is then converted into guanosine-5'-monophosphate. This gene is up-regulated in some neoplasms, suggesting it may play a role in malignant transformation. [provided by RefSeq, Jul 2008]

ENSG00000290315 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP7: Synonymous conserved (PhyloP=3.1 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000884.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH2	NM_000884.3	MANE Select	c.915C>A	p.Val305Val	synonymous	Exon 9 of 14	NP_000875.2	P12268
	IMPDH2	NM_001410759.1		c.915C>A	p.Val305Val	synonymous	Exon 9 of 15	NP_001397688.1	H0Y4R1
	IMPDH2	NM_001410760.1		c.840C>A	p.Val280Val	synonymous	Exon 8 of 14	NP_001397689.1	A0A7I2YQK5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH2	ENST00000326739.9	TSL:1 MANE Select	c.915C>A	p.Val305Val	synonymous	Exon 9 of 14	ENSP00000321584.4	P12268
	ENSG00000290315	ENST00000703936.1		c.2955C>A	p.Val985Val	synonymous	Exon 17 of 22	ENSP00000515567.1	A0A994J749
	IMPDH2	ENST00000937815.1		c.1083C>A	p.Val361Val	synonymous	Exon 9 of 14	ENSP00000607874.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.9
DANN	Benign	0.85
PhyloP100		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-49063848;