4-44704902-C-T

Variant names:

• chr4-44704902-C-T
• rs2709
• ENST00000509756.1:c.*2839G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000509756.1(GNPDA2):​c.*2839G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 981,506 control chromosomes in the GnomAD database, including 25,575 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 0.22 (3765 hom., cov: 32)
  • Exomes 𝑓: 0.23 (21810 hom.)
• Consequence: GNPDA2 ENST00000509756.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 10 publications found

Genes affected

GNPDA2 (HGNC:21526): (glucosamine-6-phosphate deaminase 2) The protein encoded by this gene is an allosteric enzyme that catalyzes the reversible reaction converting D-glucosamine-6-phosphate into D-fructose-6-phosphate and ammonium. Variations of this gene have been reported to be associated with influencing body mass index and susceptibility to obesity. A pseudogene of this gene is located on chromosome 9. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

ENSG00000272936 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000509756.1. 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
	GNPDA2	NM_138335.3	MANE Select	c.770-1760G>A		intron	N/A	NP_612208.1	Q8TDQ7-1
	GNPDA2	NM_001270880.2		c.668-1760G>A		intron	N/A	NP_001257809.1	Q8TDQ7-5
	GNPDA2	NM_001270881.2		c.560-1760G>A		intron	N/A	NP_001257810.1	Q8TDQ7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPDA2	ENST00000509756.1	TSL:1	c.*2839G>A		3_prime_UTR	Exon 6 of 6	ENSP00000424061.1	Q8TDQ7-3
	GNPDA2	ENST00000295448.8	TSL:1 MANE Select	c.770-1760G>A		intron	N/A	ENSP00000295448.3	Q8TDQ7-1
	GNPDA2	ENST00000507917.5	TSL:1	c.668-1760G>A		intron	N/A	ENSP00000425868.1	Q8TDQ7-5

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32962 AN: 151684 Hom.: 3760 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.228 AC: 189135 AN: 829704 Hom.: 21810 Cov.: 20 AF XY: 0.229 AC XY: 87765 AN XY: 383298

African (AFR) AF: 0.218 AC: 3426 AN: 15712

American (AMR) AF: 0.160 AC: 156 AN: 972

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 1395 AN: 5120

East Asian (EAS) AF: 0.218 AC: 788 AN: 3610

South Asian (SAS) AF: 0.328 AC: 5381 AN: 16386

European-Finnish (FIN) AF: 0.180 AC: 49 AN: 272

Middle Eastern (MID) AF: 0.334 AC: 539 AN: 1614

European-Non Finnish (NFE) AF: 0.225 AC: 171028 AN: 758816

Other (OTH) AF: 0.234 AC: 6373 AN: 27202

GnomAD4 genome AF: 0.217 AC: 32981 AN: 151802 Hom.: 3765 Cov.: 32 AF XY: 0.215 AC XY: 15928 AN XY: 74188

African (AFR) AF: 0.212 AC: 8775 AN: 41456

American (AMR) AF: 0.171 AC: 2608 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 913 AN: 3470

East Asian (EAS) AF: 0.211 AC: 1089 AN: 5166

South Asian (SAS) AF: 0.337 AC: 1624 AN: 4822

European-Finnish (FIN) AF: 0.155 AC: 1635 AN: 10564

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15577 AN: 67794

Other (OTH) AF: 0.227 AC: 478 AN: 2110

Alfa AF: 0.123 Hom.: 215

Bravo AF: 0.212

Asia WGS AF: 0.214 AC: 740 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.60
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2709; hg19: chr4-44706919;