rs2304471

Positions:

• chr16-8802052-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000303.3(PMM2):​c.178+142C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 659,834 control chromosomes in the GnomAD database, including 16,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3005 hom., cov: 32)
  • Exomes 𝑓: 0.22 (13007 hom.)
• Consequence: PMM2 NM_000303.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00800

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-8802052-C-A is Benign according to our data. Variant chr16-8802052-C-A is described in ClinVar as [Benign]. Clinvar id is 1234913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMM2	NM_000303.3	c.178+142C>A		intron_variant		ENST00000268261.9	NP_000294.1
PMM2	XM_047434215.1	c.6+142C>A		intron_variant			XP_047290171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMM2	ENST00000268261.9	c.178+142C>A		intron_variant		1	NM_000303.3	ENSP00000268261	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29328 AN: 151958 Hom.: 3000 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.191

GnomAD3 exomes AF: 0.219 AC: 31247 AN: 142842 Hom.: 3754 AF XY: 0.228 AC XY: 17469 AN XY: 76574

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.155

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.316

Gnomad SAS exome AF: 0.325

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.204

GnomAD4 exome AF: 0.217 AC: 110162 AN: 507758 Hom.: 13007 Cov.: 5 AF XY: 0.224 AC XY: 62068 AN XY: 276562

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.323

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.193 AC: 29360 AN: 152076 Hom.: 3005 Cov.: 32 AF XY: 0.196 AC XY: 14601 AN XY: 74328

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.194

Alfa AF: 0.196 Hom.: 938

Bravo AF: 0.187

Asia WGS AF: 0.309 AC: 1074 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.48

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: rs2304471; hg19: chr16-8895909;