rs142123453

Positions:

• chr16-8806447-G-A
• chr16-8806447-G-C

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.347+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00279 in 1,218,064 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (6 hom.)
• Consequence: PMM2 NM_000303.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.124

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-8806447-G-A is Benign according to our data. Variant chr16-8806447-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMM2	NM_000303.3	c.347+40G>A		intron_variant		ENST00000268261.9	NP_000294.1
PMM2	XM_047434215.1	c.98+40G>A		intron_variant			XP_047290171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMM2	ENST00000268261.9	c.347+40G>A		intron_variant		1	NM_000303.3	ENSP00000268261.4

Frequencies

GnomAD3 genomes AF: 0.00348 AC: 529 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00622

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00312

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00233 AC: 584 AN: 250234 Hom.: 2 AF XY: 0.00225 AC XY: 305 AN XY: 135384

Gnomad AFR exome AF: 0.00687

Gnomad AMR exome AF: 0.00125

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000895

Gnomad NFE exome AF: 0.00344

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00269 AC: 2871 AN: 1065722 Hom.: 6 Cov.: 15 AF XY: 0.00264 AC XY: 1450 AN XY: 548772

Gnomad4 AFR exome AF: 0.00643

Gnomad4 AMR exome AF: 0.00138

Gnomad4 ASJ exome AF: 0.000932

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000767

Gnomad4 FIN exome AF: 0.00117

Gnomad4 NFE exome AF: 0.00324

Gnomad4 OTH exome AF: 0.00249

GnomAD4 genome AF: 0.00349 AC: 531 AN: 152342 Hom.: 0 Cov.: 33 AF XY: 0.00317 AC XY: 236 AN XY: 74494

Gnomad4 AFR AF: 0.00625

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00312

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00191 Hom.: 0

Bravo AF: 0.00393

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.91
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs142123453; hg19: chr16-8900304;