rs137862339

chr16-8811200-T-Achr16-8811200-T-Cchr16-8811200-T-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000303.3(PMM2):c.447+22T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00659 in 1,388,566 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (2 hom., cov: 34)
  • Exomes 𝑓: 0.0068 (17 hom.)
• Consequence: PMM2 NM_000303.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.151

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-8811200-T-A is Benign according to our data. Variant chr16-8811200-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 255807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMM2	NM_000303.3	c.447+22T>A		intron_variant		ENST00000268261.9
PMM2	XM_047434215.1	c.198+22T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMM2	ENST00000268261.9	c.447+22T>A		intron_variant		1	NM_000303.3	P1

Frequencies

GnomAD3 genomes AF: 0.00526 AC: 800 AN: 152176 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.00208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00819

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00717

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00538 AC: 872 AN: 162106 Hom.: 2 AF XY: 0.00541 AC XY: 464 AN XY: 85700

Gnomad AFR exome AF: 0.00202

Gnomad AMR exome AF: 0.00338

Gnomad ASJ exome AF: 0.00967

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00116

Gnomad FIN exome AF: 0.00896

Gnomad NFE exome AF: 0.00751

Gnomad OTH exome AF: 0.00837

GnomAD4 exome AF: 0.00676 AC: 8357 AN: 1236272 Hom.: 17 Cov.: 18 AF XY: 0.00656 AC XY: 4056 AN XY: 618286

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00332

Gnomad4 ASJ exome AF: 0.00896

Gnomad4 EAS exome AF: 0.0000284

Gnomad4 SAS exome AF: 0.00102

Gnomad4 FIN exome AF: 0.00841

Gnomad4 NFE exome AF: 0.00771

Gnomad4 OTH exome AF: 0.00598

GnomAD4 genome AF: 0.00525 AC: 799 AN: 152294 Hom.: 2 Cov.: 34 AF XY: 0.00541 AC XY: 403 AN XY: 74478

Gnomad4 AFR AF: 0.00207

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.00806

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00819

Gnomad4 NFE AF: 0.00717

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00306 Hom.: 0

Bravo AF: 0.00513

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	PMM2: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 13, 2020	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.1
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs137862339; hg19: chr16-8905057;