Variant rs137862339 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.151

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.

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 GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMM2	NM_000303.3 linkuse as main transcript	c.447+22T>A		intron_variant		ENST00000268261.9	NP_000294.1
PMM2	XM_047434215.1 linkuse as main transcript	c.198+22T>A		intron_variant			XP_047290171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMM2	ENST00000268261.9 linkuse as main transcript	c.447+22T>A		intron_variant		1	NM_000303.3	ENSP00000268261	P1	O15305-1

Frequencies

GnomAD3 genomes

AF:

0.00526

AC:

800

AN:

152176

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00541

AC XY:

464

AN XY:

85700

show subpopulations

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.:

Cov.:

AF XY:

0.00656

AC XY:

4056

AN XY:

618286

show subpopulations

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.:

Cov.:

AF XY:

0.00541

AC XY:

403

AN XY:

74478

show subpopulations

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.:

Bravo

AF:

0.00513

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

- -

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

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