Genetic Variant IMPDH2:c.1296-23C>T (chr3-49024825-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000884.3(IMPDH2):c.1296-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,614,054 control chromosomes in the GnomAD database, including 142 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 0.0089 ( 8 hom., cov: 33)

Exomes 𝑓: 0.012 ( 134 hom. )

Consequence

IMPDH2
NM_000884.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.36

Publications

4 publications found

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]

IMPDH2 links:

ENSG00000290315 (HGNC:):

ENSG00000290315 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS2

High AC in GnomAd4 at 1351 AD gene.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IMPDH2	NM_000884.3	MANE Select	c.1296-23C>T	intron	N/A	NP_000875.2	P12268
IMPDH2	NM_001410759.1		c.1368-23C>T	intron	N/A	NP_001397688.1	H0Y4R1
IMPDH2	NM_001410760.1		c.1293-23C>T	intron	N/A	NP_001397689.1	A0A7I2YQK5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IMPDH2	ENST00000326739.9	TSL:1 MANE Select	c.1296-23C>T	intron	N/A	ENSP00000321584.4	P12268
ENSG00000290315	ENST00000703936.1		c.3336-23C>T	intron	N/A	ENSP00000515567.1	A0A994J749
IMPDH2	ENST00000937815.1		c.1464-23C>T	intron	N/A	ENSP00000607874.1

Frequencies

GnomAD3 genomes

AF:

0.00888

AC:

1352

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00256

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00799

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00915

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0144

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00897

AC:

2254

AN:

251222

AF XY:

0.00911

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.00567

Gnomad ASJ exome

AF:

0.00348

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00916

Gnomad NFE exome

AF:

0.0148

Gnomad OTH exome

AF:

0.00930

GnomAD4 exome

AF:

0.0124

AC:

18189

AN:

1461744

Hom.:

134

Cov.:

AF XY:

0.0123

AC XY:

8912

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.00155

AC:

AN:

33480

American (AMR)

AF:

0.00610

AC:

273

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00306

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00167

AC:

144

AN:

86242

European-Finnish (FIN)

AF:

0.00990

AC:

529

AN:

53410

Middle Eastern (MID)

AF:

0.0123

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0148

AC:

16432

AN:

1111906

Other (OTH)

AF:

0.0101

AC:

608

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1059

2118

3177

4236

5295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

604

1208

1812

2416

3020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00887

AC:

1351

AN:

152310

Hom.:

Cov.:

AF XY:

0.00806

AC XY:

600

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00255

AC:

106

AN:

41570

American (AMR)

AF:

0.00798

AC:

122

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.00166

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00915

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0144

AC:

977

AN:

68032

Other (OTH)

AF:

0.0104

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

151

226

302

377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00842

Hom.:

Bravo

AF:

0.00872

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.010

(source)

DANN

Benign

0.49

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over