chr16-8804745-G-GT

Variant names:

• chr16-8804745-G-GT
• rs145496357
• NM_000303.3:c.179-15dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000303.3(PMM2):​c.179-15dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00626 in 1,563,414 control chromosomes in the GnomAD database, including 532 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (264 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (268 hom.)
• Consequence: PMM2 NM_000303.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.28
• 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.

• BP6: Variant 16-8804745-G-GT is Benign according to our data. Variant chr16-8804745-G-GT is described in ClinVar as Benign. ClinVar VariationId is 92799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000303.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMM2	NM_000303.3	MANE Select	c.179-15dupT		intron	N/A	NP_000294.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMM2	ENST00000268261.9	TSL:1 MANE Select	c.179-22_179-21insT		intron	N/A	ENSP00000268261.4
	PMM2	ENST00000565221.5	TSL:1	n.178+2835_178+2836insT		intron	N/A	ENSP00000457932.1
	PMM2	ENST00000566540.5	TSL:1	n.179-1571_179-1570insT		intron	N/A	ENSP00000454284.1

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4966 AN: 152020 Hom.: 263 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0287

GnomAD2 exomes AF: 0.00895 AC: 2241 AN: 250340 AF XY: 0.00683

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.00684

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000327

Gnomad OTH exome AF: 0.00720

GnomAD4 exome AF: 0.00341 AC: 4815 AN: 1411278 Hom.: 268 Cov.: 27 AF XY: 0.00293 AC XY: 2069 AN XY: 705354

African (AFR) AF: 0.117 AC: 3800 AN: 32484

American (AMR) AF: 0.00721 AC: 322 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25810

East Asian (EAS) AF: 0.00 AC: 0 AN: 39428

South Asian (SAS) AF: 0.000153 AC: 13 AN: 85224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00388 AC: 22 AN: 5668

European-Non Finnish (NFE) AF: 0.000220 AC: 234 AN: 1065860

Other (OTH) AF: 0.00721 AC: 424 AN: 58786

GnomAD4 genome AF: 0.0326 AC: 4967 AN: 152136 Hom.: 264 Cov.: 32 AF XY: 0.0313 AC XY: 2326 AN XY: 74384

African (AFR) AF: 0.113 AC: 4670 AN: 41476

American (AMR) AF: 0.0139 AC: 213 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 67996

Other (OTH) AF: 0.0284 AC: 60 AN: 2110

Alfa AF: 0.00156 Hom.: 1

Bravo AF: 0.0377

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Oct 09, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PMM2-congenital disorder of glycosylation Benign:1

Sep 25, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not provided Benign:1

Feb 23, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs145496357; hg19: chr16-8898602;