chr3-49024547-CAAACTT-C

Variant names:

• chr3-49024547-CAAACTT-C
• NM_000884.3:c.1465_1470delAAGTTT

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_000884.3(IMPDH2):​c.1465_1470delAAGTTT​(p.Lys489_Phe490del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IMPDH2 NM_000884.3 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.85
• 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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000884.3.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.1465_1470delAAGTTT	p.Lys489_Phe490del	conservative_inframe_deletion	Exon 13 of 14	NP_000875.2	P12268
	IMPDH2	NM_001410759.1		c.1537_1542delAAGTTT	p.Lys513_Phe514del	conservative_inframe_deletion	Exon 14 of 15	NP_001397688.1	H0Y4R1
	IMPDH2	NM_001410760.1		c.1462_1467delAAGTTT	p.Lys488_Phe489del	conservative_inframe_deletion	Exon 13 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.1465_1470delAAGTTT	p.Lys489_Phe490del	conservative_inframe_deletion	Exon 13 of 14	ENSP00000321584.4	P12268
	ENSG00000290315	ENST00000703936.1		c.3505_3510delAAGTTT	p.Lys1169_Phe1170del	conservative_inframe_deletion	Exon 21 of 22	ENSP00000515567.1	A0A994J749
	IMPDH2	ENST00000937815.1		c.1633_1638delAAGTTT	p.Lys545_Phe546del	conservative_inframe_deletion	Exon 13 of 14	ENSP00000607874.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.8

Splicing

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

Other links and lift over

hg19: chr3-49061980;