3-49028693-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000884.3(IMPDH2):​c.147+65C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000772 in 1,296,074 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

IMPDH2
NM_000884.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0930
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IMPDH2NM_000884.3 linkc.147+65C>A intron_variant Intron 2 of 13 ENST00000326739.9 NP_000875.2 P12268A0A384N6C2
IMPDH2NM_001410759.1 linkc.147+65C>A intron_variant Intron 2 of 14 NP_001397688.1
IMPDH2NM_001410760.1 linkc.147+65C>A intron_variant Intron 2 of 13 NP_001397689.1
IMPDH2NM_001410761.1 linkc.147+65C>A intron_variant Intron 2 of 12 NP_001397690.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IMPDH2ENST00000326739.9 linkc.147+65C>A intron_variant Intron 2 of 13 1 NM_000884.3 ENSP00000321584.4 P12268
ENSG00000290315ENST00000703936.1 linkc.2187+65C>A intron_variant Intron 10 of 21 ENSP00000515567.1 A0A994J749

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.72e-7
AC:
1
AN:
1296074
Hom.:
0
Cov.:
19
AF XY:
0.00
AC XY:
0
AN XY:
652642
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000104
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
5.2
DANN
Benign
0.74

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: chr3-49066126; API