rs62031146

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000303.3(PMM2):c.324G>A(p.Ala108Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,612,270 control chromosomes in the GnomAD database, including 325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 33 hom., cov: 33)

Exomes 𝑓: 0.017 ( 292 hom. )

Consequence

PMM2
NM_000303.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -4.39

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 16-8806384-G-A is Benign according to our data. Variant chr16-8806384-G-A is described in ClinVar as [Benign]. Clinvar id is 129976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8806384-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0133 (2030/152282) while in subpopulation SAS AF= 0.0354 (171/4830). AF 95% confidence interval is 0.0311. There are 33 homozygotes in gnomad4. There are 984 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMM2	NM_000303.3 link	c.324G>A	p.Ala108Ala	synonymous_variant	Exon 4 of 8	ENST00000268261.9	NP_000294.1	O15305-1A0A0S2Z4J6Q59F02
PMM2	XM_047434215.1 link	c.75G>A	p.Ala25Ala	synonymous_variant	Exon 2 of 6		XP_047290171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMM2	ENST00000268261.9 link	c.324G>A	p.Ala108Ala	synonymous_variant	Exon 4 of 8	1	NM_000303.3	ENSP00000268261.4		O15305-1

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2029

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0172

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0352

Gnomad FIN

AF:

0.00396

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0163

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.0167

AC:

4190

AN:

251448

Hom.:

AF XY:

0.0180

AC XY:

2449

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00523

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.0481

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0345

Gnomad FIN exome

AF:

0.00522

Gnomad NFE exome

AF:

0.0175

Gnomad OTH exome

AF:

0.0181

GnomAD4 exome

AF:

0.0166

AC:

24178

AN:

1459988

Hom.:

292

Cov.:

AF XY:

0.0173

AC XY:

12534

AN XY:

726512

show subpopulations

Gnomad4 AFR exome

AF:

0.00586

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.0506

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0337

Gnomad4 FIN exome

AF:

0.00552

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.0175

GnomAD4 genome

AF:

0.0133

AC:

2030

AN:

152282

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

984

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00534

Gnomad4 AMR

AF:

0.0171

Gnomad4 ASJ

AF:

0.0521

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0354

Gnomad4 FIN

AF:

0.00396

Gnomad4 NFE

AF:

0.0163

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.0159

Hom.:

Bravo

AF:

0.0128

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0169

EpiControl

AF:

0.0183

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Sep 25, 2017

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: The PMM2 c.324G>A (p.Ala108Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SRp55. However, these predictions have yet to be confirmed by functional studies. This variant was found in 2137/121286 control chromosomes at a frequency of 0.0176195, which is approximately 3 times the estimated maximal expected allele frequency of a pathogenic PMM2 variant (0.0055902), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign. -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Jun 17, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 23, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PMM2-congenital disorder of glycosylation

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 21, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.5

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.22

Position offset: 23

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over