NM_000091.5(COL4A3):c.2417dup (p.Gly807fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 12, 2024
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:: RCV003148822.4

Allele description [Variation Report for NM_000091.5(COL4A3):c.2417dup (p.Gly807fs)]

NM_000091.5(COL4A3):c.2417dup (p.Gly807fs)

Genes:

MFF-DT:MFF divergent transcript [Gene - HGNC]
COL4A3:collagen type IV alpha 3 chain [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2q36.3

Genomic location:

Preferred name:

NM_000091.5(COL4A3):c.2417dup (p.Gly807fs)

HGVS:

NC_000002.12:g.227280935dup
NG_011591.1:g.121371dup
NM_000091.4:c.2417dup
NM_000091.5:c.2417dupMANE SELECT
NP_000082.2:p.Gly807fs
LRG_230t1:c.2417dup
LRG_230:g.121371dup
NC_000002.11:g.228145646_228145647insC
NC_000002.11:g.228145651dup
NM_000091.4:c.2417dupC

Protein change:

G807fs

Links:

dbSNP: rs1440033157

NCBI 1000 Genomes Browser:

rs1440033157

Molecular consequence:

NM_000091.5:c.2417dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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LJP_0081c AND (alive[prop]) (0)
Gene
Homo sapiens meiosis regulator for oocyte development (MIOS), transcript variant...
Homo sapiens meiosis regulator for oocyte development (MIOS), transcript variant 6, non-coding RNA
gi|1624732079|ref|NR_163250.1|

Nucleotide
Homo sapiens oxytocin/neurophysin I prepropeptide (OXT), mRNA
Homo sapiens oxytocin/neurophysin I prepropeptide (OXT), mRNA
gi|1519243997|ref|NM_000915.4|

Nucleotide
large ribosomal subunit protein uL30-like 1 [Mus musculus]
large ribosomal subunit protein uL30-like 1 [Mus musculus]
gi|27754134|ref|NP_079709.2|

Protein
slc25a4 AND (alive[prop]) (990)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003837027	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 12, 2024)	germline	clinical testing	Citation Link,
SCV004294022	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 18, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 8956999, 24854265, 26809805, 27281700, 11134255, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003837027

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Sep 12, 2024)

germline

clinical testing

Citation Link,

SCV004294022

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 18, 2023)

germline

clinical testing

PubMed (6)
[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	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Collagen COL4A3 knockout: a mouse model for autosomal Alport syndrome.

Cosgrove D, Meehan DT, Grunkemeyer JA, Kornak JM, Sayers R, Hunter WJ, Samuelson GC.

Genes Dev. 1996 Dec 1;10(23):2981-92.

PubMed [citation]

PMID:: 8956999

Improving mutation screening in familial hematuric nephropathies through next generation sequencing.

Morinière V, Dahan K, Hilbert P, Lison M, Lebbah S, Topa A, Bole-Feysot C, Pruvost S, Nitschke P, Plaisier E, Knebelmann B, Macher MA, Noel LH, Gubler MC, Antignac C, Heidet L.

J Am Soc Nephrol. 2014 Dec;25(12):2740-51. doi: 10.1681/ASN.2013080912. Epub 2014 May 22.

PubMed [citation]

PMID:: 24854265
PMCID:: PMC4243343

See all PubMed Citations (6)

Details of each submission

From GeneDx, SCV003837027.2

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 36117978, 37217505, 11134255, 38346493)

#	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, SCV004294022.1

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

Description

This sequence change creates a premature translational stop signal (p.Gly807Argfs*28) in the COL4A3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL4A3 are known to be pathogenic (PMID: 8956999, 24854265, 26809805, 27281700). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Alport syndrome (PMID: 11134255). ClinVar contains an entry for this variant (Variation ID: 552236). 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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