NM_172351.3(CD46):c.198A>T (p.Lys66Asn) AND Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 27, 2021
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:: RCV001543667.1

Allele description [Variation Report for NM_172351.3(CD46):c.198A>T (p.Lys66Asn)]

NM_172351.3(CD46):c.198A>T (p.Lys66Asn)

Gene:

CD46:CD46 molecule [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q32.2

Genomic location:

Preferred name:

NM_172351.3(CD46):c.198A>T (p.Lys66Asn)

Other names:

p.Lys66Asn

HGVS:

NC_000001.11:g.207757114A>T
NG_009296.1:g.10058A>T
NM_002389.4:c.198A>T
NM_153826.4:c.198A>T
NM_172350.3:c.198A>T
NM_172351.3:c.198A>TMANE SELECT
NM_172352.3:c.198A>T
NM_172353.3:c.198A>T
NM_172355.3:c.198A>T
NM_172356.3:c.198A>T
NM_172357.3:c.198A>T
NM_172358.3:c.198A>T
NM_172359.3:c.198A>T
NM_172361.3:c.198A>T
NP_002380.3:p.Lys66Asn
NP_722548.1:p.Lys66Asn
NP_758860.1:p.Lys66Asn
NP_758861.1:p.Lys66Asn
NP_758862.1:p.Lys66Asn
NP_758863.1:p.Lys66Asn
NP_758865.1:p.Lys66Asn
NP_758866.1:p.Lys66Asn
NP_758867.1:p.Lys66Asn
NP_758868.1:p.Lys66Asn
NP_758869.1:p.Lys66Asn
NP_758871.1:p.Lys66Asn
LRG_155t1:c.198A>T
LRG_155:g.10058A>T
LRG_155p1:p.Lys66Asn
NC_000001.10:g.207930459A>T

Protein change:

K66N

Links:

dbSNP: rs150429980

Molecular consequence:

NM_002389.4:c.198A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153826.4:c.198A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172350.3:c.198A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172351.3:c.198A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172352.3:c.198A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172353.3:c.198A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172355.3:c.198A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172356.3:c.198A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172357.3:c.198A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172358.3:c.198A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172359.3:c.198A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172361.3:c.198A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly
Synonyms:: HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 2; AHUS, SUSCEPTIBILITY TO, 2
Identifiers:: MONDO: MONDO:0013040; MedGen: C2752040; Orphanet: 2134; OMIM: 612922

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001762353	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 27, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26054645, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001762353

Johns Hopkins Genomics, Johns Hopkins University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 27, 2021)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Complement regulator CD46: genetic variants and disease associations.

Liszewski MK, Atkinson JP.

Hum Genomics. 2015 Jun 10;9(1):7. doi: 10.1186/s40246-015-0029-z. Review.

PubMed [citation]

PMID:: 26054645
PMCID:: PMC4469999

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 Johns Hopkins Genomics, Johns Hopkins University, SCV001762353.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

CD46 c.198A>G (rs150429980) is rare (<0.1%) in a large population dataset (gnomAD: 106/282834 total alleles; 0.04%; no homozygotes) and has not been reported in ClinVar. It has not been reported in the literature in individuals with atypical hemolytic anemia syndrome, to our knowledge. Of three bioinformatics tools queried, one predicts that the substitution would be damaging, while two predict that it would be tolerated. The lysine residue at this position is evolutionarily conserved across a subset of the mammalian species assessed. We consider the clinical significance of CD46 c.198A>G to be uncertain at this time.

#	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: Feb 15, 2026

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