rs11706052

chr3-49026677-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000884.3(IMPDH2):c.819+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 1,613,738 control chromosomes in the GnomAD database, including 8,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.076 (575 hom., cov: 33)
  • Exomes 𝑓: 0.099 (7640 hom.)
• Consequence: IMPDH2 NM_000884.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.998

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-49026677-A-G is Benign according to our data. Variant chr3-49026677-A-G is described in ClinVar as [Benign]. Clinvar id is 1229935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMPDH2	NM_000884.3	c.819+10T>C		intron_variant		ENST00000326739.9
IMPDH2	NM_001410759.1	c.819+10T>C		intron_variant
IMPDH2	NM_001410760.1	c.744+10T>C		intron_variant
IMPDH2	NM_001410761.1	c.744+10T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMPDH2	ENST00000326739.9	c.819+10T>C		intron_variant		1	NM_000884.3	P1

Frequencies

GnomAD3 genomes AF: 0.0757 AC: 11511 AN: 152158 Hom.: 575 Cov.: 33

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0706

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0379

Gnomad SAS AF: 0.0605

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0824

GnomAD3 exomes AF: 0.0834 AC: 20969 AN: 251340 Hom.: 1011 AF XY: 0.0840 AC XY: 11410 AN XY: 135856

Gnomad AFR exome AF: 0.0205

Gnomad AMR exome AF: 0.0481

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.0379

Gnomad SAS exome AF: 0.0569

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.0933

GnomAD4 exome AF: 0.0991 AC: 144841 AN: 1461460 Hom.: 7640 Cov.: 33 AF XY: 0.0979 AC XY: 71177 AN XY: 727058

Gnomad4 AFR exome AF: 0.0182

Gnomad4 AMR exome AF: 0.0510

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.0424

Gnomad4 SAS exome AF: 0.0578

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.0908

GnomAD4 genome AF: 0.0756 AC: 11512 AN: 152278 Hom.: 575 Cov.: 33 AF XY: 0.0760 AC XY: 5657 AN XY: 74446

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.0706

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.0382

Gnomad4 SAS AF: 0.0606

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0819

Alfa AF: 0.0980 Hom.: 962

Bravo AF: 0.0694

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

IMPDH2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	1.4
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11706052; hg19: chr3-49064110; COSMIC: COSV58707418; COSMIC: COSV58707418;