rs137862339

Variant names:

• chr16-8811200-T-A
• rs137862339
• NM_000303.3:c.447+22T>A

Your query was ambiguous. Multiple possible variants found:

• chr16-8811200-T-A
• chr16-8811200-T-C
• chr16-8811200-T-G

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: 0.151
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 255807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMM2	NM_000303.3	c.447+22T>A		intron_variant	Intron 5 of 7	ENST00000268261.9	NP_000294.1
PMM2	XM_047434215.1	c.198+22T>A		intron_variant	Intron 3 of 5		XP_047290171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMM2	ENST00000268261.9	c.447+22T>A		intron_variant	Intron 5 of 7	1	NM_000303.3	ENSP00000268261.4

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

GnomAD2 exomes AF: 0.00538 AC: 872 AN: 162106 AF XY: 0.00541

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 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

African (AFR) AF: 0.00119 AC: 34 AN: 28660

American (AMR) AF: 0.00332 AC: 119 AN: 35870

Ashkenazi Jewish (ASJ) AF: 0.00896 AC: 219 AN: 24440

East Asian (EAS) AF: 0.0000284 AC: 1 AN: 35220

South Asian (SAS) AF: 0.00102 AC: 78 AN: 76520

European-Finnish (FIN) AF: 0.00841 AC: 412 AN: 48996

Middle Eastern (MID) AF: 0.00446 AC: 24 AN: 5378

European-Non Finnish (NFE) AF: 0.00771 AC: 7155 AN: 928480

Other (OTH) AF: 0.00598 AC: 315 AN: 52708

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

African (AFR) AF: 0.00207 AC: 86 AN: 41554

American (AMR) AF: 0.00569 AC: 87 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4820

European-Finnish (FIN) AF: 0.00819 AC: 87 AN: 10622

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00717 AC: 488 AN: 68028

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00306 Hom.: 0

Bravo AF: 0.00513

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PMM2: BS2 -

Feb 13, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.63
PhyloP100		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs137862339; hg19: chr16-8905057;