rs28595449

chr16-8814388-C-Gchr16-8814388-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMM2	NM_000303.3	c.639+1282C>G		intron_variant		ENST00000268261.9
PMM2	XM_047434215.1	c.390+1282C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMM2	ENST00000268261.9	c.639+1282C>G		intron_variant		1	NM_000303.3	P1

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

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.233

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.45
Dann	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs28595449; hg19: chr16-8908245;