NM_033380.3(COL4A5):c.647G>A (p.Gly216Glu) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 13, 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:: RCV000681889.16

Allele description [Variation Report for NM_033380.3(COL4A5):c.647G>A (p.Gly216Glu)]

NM_033380.3(COL4A5):c.647G>A (p.Gly216Glu)

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.647G>A (p.Gly216Glu)

HGVS:

NC_000023.11:g.108578079G>A
NG_011977.2:g.143156G>A
NM_000495.5:c.647G>A
NM_033380.3:c.647G>AMANE SELECT
NP_000486.1:p.Gly216Glu
NP_203699.1:p.Gly216Glu
LRG_232t1:c.647G>A
LRG_232t2:c.647G>A
LRG_232:g.143156G>A
LRG_232p1:p.Gly216Glu
LRG_232p2:p.Gly216Glu
NC_000023.10:g.107821309G>A
NG_011977.1:g.143156G>A

Protein change:

G216E

Links:

dbSNP: rs104886074

NCBI 1000 Genomes Browser:

rs104886074

Molecular consequence:

NM_000495.5:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033380.3:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Homo sapiens secretin (SCT), mRNA
Homo sapiens secretin (SCT), mRNA
gi|11345449|ref|NM_021920.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000809368	Gharavi Laboratory, Columbia University	no assertion criteria provided (ACMG Guidelines, 2015)	Pathogenic (Sep 16, 2018)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV001577489	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 13, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20378821, 22921432, 8738805, 17660027, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000809368

Gharavi Laboratory, Columbia University

no assertion criteria provided

(ACMG Guidelines, 2015)

Pathogenic
(Sep 16, 2018)

germline

research

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

SCV001577489

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 13, 2023)

germline

clinical testing

PubMed (5)
[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	not provided	not provided	not provided	not provided	not provided	research
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

Genotype-phenotype correlation in X-linked Alport syndrome.

Bekheirnia MR, Reed B, Gregory MC, McFann K, Shamshirsaz AA, Masoumi A, Schrier RW.

J Am Soc Nephrol. 2010 May;21(5):876-83. doi: 10.1681/ASN.2009070784. Epub 2010 Apr 8.

PubMed [citation]

PMID:: 20378821
PMCID:: PMC2865738

See all PubMed Citations (6)

Details of each submission

From Gharavi Laboratory, Columbia University, SCV000809368.1

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

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001577489.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 216 of the COL4A5 protein (p.Gly216Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with X-linked Alport syndrome (PMID: 20378821, 22921432; Invitae). ClinVar contains an entry for this variant (Variation ID: 562417). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the p.Gly216 amino acid residue in COL4A5. Other variant(s) that disrupt this residue have been observed in individuals with COL4A5-related conditions (PMID: 8738805, 17660027), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

#	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 13, 2024

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