NM_001735.3(C5):c.55C>T (p.Gln19Ter) AND Complement component 5 deficiency

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 16, 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:: RCV000018578.31

Allele description [Variation Report for NM_001735.3(C5):c.55C>T (p.Gln19Ter)]

NM_001735.3(C5):c.55C>T (p.Gln19Ter)

Gene:

C5:complement C5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q33.2

Genomic location:

Preferred name:

NM_001735.3(C5):c.55C>T (p.Gln19Ter)

Other names:

C5, GLN84TER; Q84*

HGVS:

NC_000009.12:g.121050192G>A
NG_007364.1:g.5085C>T
NM_001317163.2:c.84-3809C>T
NM_001317164.2:c.55C>T
NM_001735.3:c.55C>TMANE SELECT
NP_001304093.1:p.Gln19Ter
NP_001726.2:p.Gln19Ter
NP_001726.2:p.Gln19Ter
LRG_28t1:c.55C>T
LRG_28:g.5085C>T
LRG_28p1:p.Gln19Ter
NC_000009.11:g.123812470G>A
NM_001735.2:c.55C>T

Protein change:

Q19*; GLN84TER

Links:

OMIM: 120900.0001; dbSNP: rs121909587

NCBI 1000 Genomes Browser:

rs121909587

Molecular consequence:

NM_001317163.2:c.84-3809C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001317164.2:c.55C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001735.3:c.55C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Complement component 5 deficiency
Synonyms:: Leiner disease; C5 deficiency; Dysfunction of the fifth component of complement (C5)
Identifiers:: MONDO: MONDO:0012295; MedGen: C0343047; OMIM: 609536

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000038861	OMIM	no assertion criteria provided	Pathogenic (May 15, 1995)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV003834805	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 16, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004848103	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 28, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 7730648, 23371790, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000038861

OMIM

no assertion criteria provided

Pathogenic
(May 15, 1995)

germline

literature only

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

SCV003834805

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 16, 2022)

unknown

clinical testing

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

SCV004848103

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 28, 2017)

germline

clinical testing

PubMed (3)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Inherited human complement C5 deficiency. Nonsense mutations in exons 1 (Gln1 to Stop) and 36 (Arg1458 to Stop) and compound heterozygosity in three African-American families.

Wang X, Fleischer DT, Whitehead WT, Haviland DL, Rosenfeld SI, Leddy JP, Snyderman R, Wetsel RA.

J Immunol. 1995 May 15;154(10):5464-71.

PubMed [citation]

PMID:: 7730648

C5 complement deficiency in a Saudi family, molecular characterization of mutation and literature review.

Arnaout R, Al Shorbaghi S, Al Dhekri H, Al-Mousa H, Al Ghonaium A, Al Saud B, Al Muhsen S, Al Baik L, Hawwari A.

J Clin Immunol. 2013 May;33(4):871-5. doi: 10.1007/s10875-013-9872-7. Epub 2013 Feb 1. Review.

PubMed [citation]

PMID:: 23371790

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000038861.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In affected members of an African American family with C5 deficiency (609536), Wang et al. (1995) identified a C-to-T transition in exon 1 of the C5 gene, resulting in a glutamine-to-stop substitution at codon 84 (Q84X), the first amino acid of the C5 beta chain. This mutation was identified in heterozygosity. The second mutation was not identified.

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

From Baylor Genetics, SCV003834805.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848103.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.Gln19X variant in C5 has been reported in 3 families with C5 complement deficiency. In 1 family, the 2 affected members carried the variant in the homozygous state (Arnaout 2013), whereas in the remaining 2 families (Wang 1995, reported as(C84 AG to TAG) ) the variant was found in the heterozygous state in 6 affected individuals (presumably a second undetected variant was present on the other allele) . This variant has also been identified in 0.12% (29/24,032) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs121909587). This nonsense variant leads to a premature termination codon at position 19, which is predicted to lead to a truncated or absent protein. In summary, this variant meets criteria to be classified as pathogenic for C5 complement deficiency in an autosomal recessive manner based upon biallelic case observations, segregation studies and the nature of the variant (nonsense).

#	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: Oct 8, 2024

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