NM_000303.3:c.639+1282C>G

Variant names:

• chr16-8814388-C-G
• rs28595449
• NM_000303.3:c.639+1282C>G

Variant summary

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

The NM_000303.3(PMM2):​c.639+1282C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,052 control chromosomes in the GnomAD database, including 4,338 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 0.23 (4338 hom., cov: 32)
• Consequence: PMM2 NM_000303.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942
• Publications: 3 publications found

Genes affected

PMM2 (HGNC:9115): (phosphomannomutase 2) The protein encoded by this gene catalyzes the isomerization of mannose 6-phosphate to mannose 1-phosphate, which is a precursor to GDP-mannose necessary for the synthesis of dolichol-P-oligosaccharides. Mutations in this gene have been shown to cause defects in glycoprotein biosynthesis, which manifests as carbohydrate-deficient glycoprotein syndrome type I. [provided by RefSeq, Jul 2008]

PMM2 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation type I

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• PMM2-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• hyperinsulinemic hypoglycemia with polycystic kidney disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000303.3. 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
	PMM2	NM_000303.3	MANE Select	c.639+1282C>G		intron	N/A	NP_000294.1	A0A0S2Z4J6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMM2	ENST00000268261.9	TSL:1 MANE Select	c.639+1282C>G		intron	N/A	ENSP00000268261.4	O15305-1
	PMM2	ENST00000565221.5	TSL:1	n.*257+1282C>G		intron	N/A	ENSP00000457932.1	H3BV34
	PMM2	ENST00000566540.5	TSL:1	n.*261+1282C>G		intron	N/A	ENSP00000454284.1	H3BM92

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34804 AN: 151934 Hom.: 4334 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.229 AC: 34824 AN: 152052 Hom.: 4338 Cov.: 32 AF XY: 0.234 AC XY: 17418 AN XY: 74298

African (AFR) AF: 0.141 AC: 5844 AN: 41496

American (AMR) AF: 0.212 AC: 3233 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3468

East Asian (EAS) AF: 0.320 AC: 1645 AN: 5148

South Asian (SAS) AF: 0.333 AC: 1603 AN: 4808

European-Finnish (FIN) AF: 0.298 AC: 3155 AN: 10574

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17892 AN: 67964

Other (OTH) AF: 0.233 AC: 493 AN: 2112

Alfa AF: 0.246 Hom.: 599

Bravo AF: 0.214

Asia WGS AF: 0.313 AC: 1086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.59
PhyloP100		-0.94
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: rs28595449; hg19: chr16-8908245;