NM_016579.4(CD320):c.256GAG[2] (p.Glu88del) AND CD320-related disorder

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 20, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003398922.4

Allele description

NM_016579.4(CD320):c.256GAG[2] (p.Glu88del)

Gene:

CD320:CD320 molecule [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_016579.4(CD320):c.256GAG[2] (p.Glu88del)

HGVS:

NC_000019.10:g.8305035CTC[2]
NC_000019.9:g.8369919_8369921del
NG_028124.1:g.8314GAG[2]
NM_001165895.2:c.143-955GAG[2]
NM_016579.4:c.256GAG[2]MANE SELECT
NP_057663.1:p.Glu88del
NC_000019.10:g.8305035CTC[2]
NC_000019.9:g.8369919CTC[2]
NC_000019.9:g.8369919_8369921del
NC_000019.9:g.8369919_8369921delCTC
NM_016579.3:c.262_264del
NM_016579.3:c.262_264delGAG

Protein change:

E88del

Links:

OMIM: 606475.0001; dbSNP: rs150384171

NCBI 1000 Genomes Browser:

rs150384171

Molecular consequence:

NM_016579.4:c.256GAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001165895.2:c.143-955GAG[2] - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: CD320-related disorder
Synonyms:: CD320-related condition
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004105179	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 20, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004105179

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 20, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004105179.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The CD320 c.262_264delGAG variant is predicted to result in an in-frame deletion (p.Glu88del). This variant has been reported in the homozygous or compound heterozygous state in patients with methylmalonic acidemia and homocysteinemia due to transcobalamin receptor deficiency (e.g., Quadros et al. 2010. PubMed ID: 20524213; Karth et al. 2012. PubMed ID: 22819238; Hannah-Shmouni et al. 2018. PubMed ID: 29663633; Pappas et al. 2022. PubMed ID: 34978764). Fibroblast cells from patients apparently homozygous for the CD320 c.262_264del (p.Glu88del) variant showed reduced uptake of holo-transcobalamin (holo-TC) as well as elevated levels of homocysteine and methylmalonic acid in culture medium (Quadros et al. 2010. PubMed ID: 20524213; Pangilinan et al. 2022. PubMed ID: 35107211). The c.262_264del variant has been reported in a large population database at an allele frequency of up to ~1.4%, which would be high for an autosomal recessive disorder with a severe phenotype (http://gnomad.broadinstitute.org/variant/19-8369918-ACTC-A). It should be noted, however, that most reported patients with transcobalamin receptor deficiency have been clinically asymptomatic. These data suggest that this may possibly be a benign biochemical phenotype, although the long-term outcome in these individuals is not currently well understood (Hannah-Shmouni et al. 2018. PubMed ID: 29663633). In summary, we classify the c.262_264del (p.Glu88del) variant as likely pathogenic for recessive transcobalamin receptor deficiency.

#	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: Sep 29, 2024

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