NM_033380.3(COL4A5):c.2732G>A (p.Gly911Glu) AND X-linked Alport syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 1, 2022
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:: RCV002283810.1

Allele description [Variation Report for NM_033380.3(COL4A5):c.2732G>A (p.Gly911Glu)]

NM_033380.3(COL4A5):c.2732G>A (p.Gly911Glu)

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.2732G>A (p.Gly911Glu)

HGVS:

NC_000023.11:g.108621857G>A
NG_011977.2:g.186934G>A
NM_000495.5:c.2732G>A
NM_033380.3:c.2732G>AMANE SELECT
NP_000486.1:p.Gly911Glu
NP_203699.1:p.Gly911Glu
LRG_232t1:c.2732G>A
LRG_232t2:c.2732G>A
LRG_232:g.186934G>A
LRG_232p1:p.Gly911Glu
LRG_232p2:p.Gly911Glu
NC_000023.10:g.107865087G>A
NG_011977.1:g.186934G>A
NM_000495.4:c.2732G>A
P29400:p.Gly911Glu

Protein change:

G911E

Links:

UniProtKB: P29400#VAR_011260; dbSNP: rs104886363

NCBI 1000 Genomes Browser:

rs104886363

Molecular consequence:

NM_000495.5:c.2732G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033380.3:c.2732G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV002572913	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 1, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10684360, 29204651, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002572913

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 1, 2022)

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	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Mutational analysis of COL4A5 gene in Korean Alport syndrome.

Cheong HI, Park HW, Ha IS, Choi Y.

Pediatr Nephrol. 2000 Feb;14(2):117-21.

PubMed [citation]

PMID:: 10684360

Whole-Exome Sequencing in Adults With Chronic Kidney Disease: A Pilot Study.

Lata S, Marasa M, Li Y, Fasel DA, Groopman E, Jobanputra V, Rasouly H, Mitrotti A, Westland R, Verbitsky M, Nestor J, Slater LM, D'Agati V, Zaniew M, Materna-Kiryluk A, Lugani F, Caridi G, Rampoldi L, Mattoo A, Newton CA, Rao MK, Radhakrishnan J, et al.

Ann Intern Med. 2018 Jan 16;168(2):100-109. doi: 10.7326/M17-1319. Epub 2017 Dec 5. Erratum in: Ann Intern Med. 2018 Feb 20;168(4):308. doi: 10.7326/L18-0035.

PubMed [citation]

PMID:: 29204651
PMCID:: PMC5947852

See all PubMed Citations (3)

Details of each submission

From 3billion, SCV002572913.1

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

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: 0.98). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with COL4A5 -related disorder (PMID: 10684360). A different missense change at the same codon (p.Gly911Arg) has been reported to be associated with COL4A5 -related disorder (PMID: 29204651). 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	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 12, 2024

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