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:

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002058994	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 3, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] PMID:15771971,
SCV003244594	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15771971, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002058994

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 3, 2022)

germline

clinical testing

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

PMID:15771971,

SCV003244594

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 13, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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