NM_033380.3(COL4A5):c.2422G>A (p.Gly808Arg) AND X-linked Alport syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 23, 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:: RCV003152948.1

Allele description [Variation Report for NM_033380.3(COL4A5):c.2422G>A (p.Gly808Arg)]

NM_033380.3(COL4A5):c.2422G>A (p.Gly808Arg)

Gene:

COL4A5:collagen type IV alpha 5 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq22.3

Genomic location:

Preferred name:

NM_033380.3(COL4A5):c.2422G>A (p.Gly808Arg)

HGVS:

NC_000023.11:g.108614937G>A
NG_011977.2:g.180014G>A
NM_000495.5:c.2422G>A
NM_033380.3:c.2422G>AMANE SELECT
NP_000486.1:p.Gly808Arg
NP_203699.1:p.Gly808Arg
LRG_232t1:c.2422G>A
LRG_232t2:c.2422G>A
LRG_232:g.180014G>A
LRG_232p1:p.Gly808Arg
LRG_232p2:p.Gly808Arg
NC_000023.10:g.107858167G>A

Protein change:

G808R

Molecular consequence:

NM_000495.5:c.2422G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033380.3:c.2422G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: X-linked Alport syndrome (ATS1)
Synonyms:: NEPHROPATHY AND DEAFNESS, X-LINKED; Alport syndrome 1, X-linked recessive; Alport Syndrome and Thin Basement Membrane Nephropathy
Identifiers:: MONDO: MONDO:0010520; MedGen: C4746986; Orphanet: 63; Orphanet: 88917; OMIM: 301050

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003841525	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 23, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10094548, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003841525

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 23, 2023)

unknown

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

Citations

PubMed

Detection of mutations in COL4A5 in patients with Alport syndrome.

Plant KE, Green PM, Vetrie D, Flinter FA.

Hum Mutat. 1999;13(2):124-32.

PubMed [citation]

PMID:: 10094548

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 3billion, SCV003841525.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.99; 3Cnet: 0.94). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with COL4A5-related disorder (3billion dataset). A different missense change at the same codon (p.Gly808Glu) has been reported to be associated with COL4A5-related disorder (ClinVar ID: VCV001412850 / PMID: 10094548). Therefore, this variant is classified as Likely pathogenic 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	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 5, 2023

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