NM_000092.5(COL4A4):c.81_86del (p.27IL[1]) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Jan 24, 2025
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:: RCV000483576.15

Allele description [Variation Report for NM_000092.5(COL4A4):c.81_86del (p.27IL[1])]

NM_000092.5(COL4A4):c.81_86del (p.27IL[1])

Gene:

COL4A4:collagen type IV alpha 4 chain [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2q36.3

Genomic location:

Preferred name:

NM_000092.5(COL4A4):c.81_86del (p.27IL[1])

Other names:

p.Ile29_Leu30del

HGVS:

NC_000002.12:g.227144546_227144551del
NG_011592.1:g.25011_25016del
NM_000092.5:c.81_86delMANE SELECT
NP_000083.3:p.27IL[1]
NP_000083.3:p.27_28IL[1]
LRG_231t1:c.81_86del
LRG_231:g.25011_25016del
LRG_231p1:p.27_28IL[1]
NC_000002.11:g.228009260_228009265del
NC_000002.11:g.228009262_228009267del
NM_000092.4:c.81_86del
NM_000092.4:c.81_86delACTCAT
NM_000092.5:c.81_86delACTCATMANE SELECT

Links:

dbSNP: rs771943519

NCBI 1000 Genomes Browser:

rs771943519

Molecular consequence:

NM_000092.5:c.81_86del - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000568823	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Dec 18, 2024)	germline	clinical testing	Citation Link,
SCV001232186	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 24, 2025)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 24052634, 24854265, 26809805, 28632965, 28844315, 28492532
SCV003834451	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 8, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005413561	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 14, 2024)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 24052634, 24854265, 26809805, 28844315, 33772369, 34746741, 25741868

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	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Frequent COL4 mutations in familial microhematuria accompanied by later-onset Alport nephropathy due to focal segmental glomerulosclerosis.

Papazachariou L, Papagregoriou G, Hadjipanagi D, Demosthenous P, Voskarides K, Koutsofti C, Stylianou K, Ioannou P, Xydakis D, Tzanakis I, Papadaki A, Kallivretakis N, Nikolakakis N, Perysinaki G, Gale DP, Diamantopoulos A, Goudas P, Goumenos D, Soloukides A, Boletis I, Melexopoulou C, Georgaki E, et al.

Clin Genet. 2017 Nov;92(5):517-527. doi: 10.1111/cge.13077. Epub 2017 Sep 25.

PubMed [citation]

PMID:: 28632965

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (9)

Details of each submission

From GeneDx, SCV000568823.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

In-frame deletion of two amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24052634, 35759000, 28632965, 34758253, 36938085, 37248651, Kim2021[case report], 34746741, 28844315, 26809805, 33772369)

#	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, SCV001232186.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This variant, c.81_86del, results in the deletion of 2 amino acid(s) of the COL4A4 protein (p.Ile29_Leu30del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs771943519, gnomAD 0.01%). This variant has been observed in individuals with autosomal dominant and recessive Alport syndrome and/or thin basement membrane nephropathy and hematuria (PMID: 24052634, 24854265, 26809805, 28632965, 28844315; internal data). This variant is also known as p.Ile27_Ile29delinsIle. ClinVar contains an entry for this variant (Variation ID: 369962). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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

From Revvity Omics, Revvity, SCV003834451.2

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV005413561.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (7)

Description

PM2, PM3_strong, PM4, PS4

#	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		1	not provided	not provided	not provided

Last Updated: May 16, 2025

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