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NM_003859.3(DPM1):c.506A>G (p.Asn169Ser) AND Congenital disorder of glycosylation type 1E

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Aug 13, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001808420.11

Allele description [Variation Report for NM_003859.3(DPM1):c.506A>G (p.Asn169Ser)]

NM_003859.3(DPM1):c.506A>G (p.Asn169Ser)

Genes:
ADNP-AS1:ADNP antisense RNA 1 [Gene - HGNC]
DPM1:dolichyl-phosphate mannosyltransferase subunit 1, catalytic [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20q13.13
Genomic location:
Preferred name:
NM_003859.3(DPM1):c.506A>G (p.Asn169Ser)
HGVS:
  • NC_000020.11:g.50940922T>C
  • NG_008923.1:g.22602A>G
  • NM_001317034.1:c.611A>G
  • NM_001317035.1:c.587A>G
  • NM_001317036.1:c.494+1109A>G
  • NM_003859.3:c.506A>GMANE SELECT
  • NP_001303963.1:p.Asn204Ser
  • NP_001303964.1:p.Asn196Ser
  • NP_003850.1:p.Asn169Ser
  • NP_003850.1:p.Asn169Ser
  • NC_000020.10:g.49557459T>C
  • NR_133648.2:n.537A>G
Protein change:
N169S
Links:
dbSNP: rs727503905
NCBI 1000 Genomes Browser:
rs727503905
Molecular consequence:
  • NM_001317036.1:c.494+1109A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001317034.1:c.611A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317035.1:c.587A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003859.3:c.506A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_133648.2:n.537A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Name:
Congenital disorder of glycosylation type 1E (CDG1E)
Synonyms:
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ie; CDG Ie; CDG 1E; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0012123; MedGen: C1837396; Orphanet: 79322; OMIM: 608799

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV0020589943billion
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Jan 3, 2022)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

PMID:15771971,

SCV003244594Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Aug 13, 2022)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

[Molecular diagnosis of congenital disorders of glycosylation].

Vuillaumier-Barrot S.

Ann Biol Clin (Paris). 2005 Mar-Apr;63(2):135-43. Review. French.

PubMed [citation]
PMID:
15771971
See all PubMed Citations (3)

Details of each submission

From 3billion, SCV002058994.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

Same nucleotide change resulting in same amino acid change has been previously reported to be associated with DPM1 related disorder (PMID:15771971, PS1_P). In silico tool predictions suggest damaging effect of the variant on gene or gene product (3CNET: 0.752, PP3_P). A missense variant is a common mechanism associated with Congenital disorder of glycosylation (PP2_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000004, PM2_M). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003244594.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 169 of the DPM1 protein (p.Asn169Ser). This variant is present in population databases (rs727503905, gnomAD 0.01%). This missense change has been observed in individual(s) with congenital disorder of glycosylation type 1e (PMID: 15771971). ClinVar contains an entry for this variant (Variation ID: 167008). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 30, 2024