NM_138477.4(CDAN1):c.2062C>T (p.Arg688Trp) AND Anemia, congenital dyserythropoietic, type 1a

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Dec 5, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV003144737.5

Allele description [Variation Report for NM_138477.4(CDAN1):c.2062C>T (p.Arg688Trp)]

NM_138477.4(CDAN1):c.2062C>T (p.Arg688Trp)

Gene:

CDAN1:codanin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q15.2

Genomic location:

Preferred name:

NM_138477.4(CDAN1):c.2062C>T (p.Arg688Trp)

HGVS:

NC_000015.10:g.42730710G>A
NG_012491.1:g.11510C>T
NG_130888.1:g.155G>A
NM_138477.4:c.2062C>TMANE SELECT
NP_612486.2:p.Arg688Trp
LRG_1164t1:c.2062C>T
LRG_1164:g.11510C>T
LRG_1164p1:p.Arg688Trp
NC_000015.9:g.43022908G>A
NM_138477.2:c.2062C>T

Protein change:

R688W

Molecular consequence:

NM_138477.4:c.2062C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Anemia, congenital dyserythropoietic, type 1a (CDAN1A)
Synonyms:: DYSERYTHROPOIETIC ANEMIA, CONGENITAL, TYPE Ia
Identifiers:: MONDO: MONDO:0009135; MedGen: C5574667; OMIM: 224120

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003829419	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 5, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004046124	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	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

SCV003829419

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 5, 2022)

germline

clinical testing

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

SCV004046124

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

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	yes	not provided	not provided	not provided	not provided	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

Details of each submission

From Revvity Omics, Revvity, SCV003829419.2

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

#	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

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV004046124.1

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

Description

This variant has been previously reported in the compound heterozygous state in an individual with Congenital Dyserythropoietic Anemia Type Ia (variant is referred to as c.2067C>T; p.Arg687Trp) reported to have a severe manifestation of the disease that included severe neonatal onset anemia and bone abnormalities (PMID: 16098079). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.0008% (2/246074) and thus is presumed to be rare. The c.2062C>T (p.Arg688Trp) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.2062C>T (p.Arg688Trp) variant is classified as Likely Pathogenic.

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

Last Updated: Mar 16, 2024

ClinVar

Relating variation to medicine