NM_000092.5(COL4A4):c.4708G>A (p.Glu1570Lys) AND Autosomal recessive Alport syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 10, 2021
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:: RCV000859980.5

Allele description [Variation Report for NM_000092.5(COL4A4):c.4708G>A (p.Glu1570Lys)]

NM_000092.5(COL4A4):c.4708G>A (p.Glu1570Lys)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2q36.3

Genomic location:

Preferred name:

NM_000092.5(COL4A4):c.4708G>A (p.Glu1570Lys)

HGVS:

NC_000002.12:g.227008119C>T
NG_011592.1:g.161441G>A
NM_000092.5:c.4708G>AMANE SELECT
NP_000083.3:p.Glu1570Lys
NP_000083.3:p.Glu1570Lys
LRG_231t1:c.4708G>A
LRG_231:g.161441G>A
LRG_231p1:p.Glu1570Lys
NC_000002.11:g.227872835C>T
NM_000092.4:c.4708G>A

Protein change:

E1570K

Links:

dbSNP: rs757328549

NCBI 1000 Genomes Browser:

rs757328549

Molecular consequence:

NM_000092.5:c.4708G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

probably has functional consequence

Condition(s)

Name:: Autosomal recessive Alport syndrome (ATS2)
Synonyms:: Alport syndrome recessive type; Nephropathy and deafness; ALPORT SYNDROME 2, AUTOSOMAL RECESSIVE; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008762; MedGen: C4746745; Orphanet: 63; Orphanet: 88919; OMIM: 203780

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000920872	Division of Nephrology, Beth Israel Deaconess Medical Center	no assertion criteria provided	Likely pathogenic	unknown	provider interpretation
SCV002060099	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))	Uncertain significance (Nov 10, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000920872

Division of Nephrology, Beth Israel Deaconess Medical Center

no assertion criteria provided

Likely pathogenic

unknown

provider interpretation

SCV002060099

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))

Uncertain significance
(Nov 10, 2021)

unknown

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	1	not provided	not provided	not provided	not provided	provider interpretation
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Autosomal Recessive Alport Syndrome Unveiled by Pregnancy.

Drury ER, Stillman IE, Pollak MR, Denker BM.

Nephron. 2019;143(4):288-292. doi: 10.1159/000502147. Epub 2019 Aug 13.

PubMed [citation]

PMID:: 31408864
PMCID:: PMC7082947

Details of each submission

From Division of Nephrology, Beth Israel Deaconess Medical Center, SCV000920872.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		1	not provided	not provided	provider interpretation (GTR000515481.1)	not provided

Description

The c.4708G>A variant in COL4A4 was observed along with another COL4A4 variant, c.3861delinsCTC, in a female patient with clinical and renal biopsy findings consistent with Alport Syndrome. This patient was interpreted as being compound heterozygous for variants causing autosomal recessive Alport Syndrome. This patient had a relatively mild phenotype. This case manuscript is under revision for publication.

#	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	(GTR000515481.1)	1	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV002060099.2

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

Description

NM_000092.4(COL4A4):c.4708G>A(E1570K) is a missense variant classified as a variant of uncertain significance in the context of COL4A4-related Alport syndrome. E1570K has been observed in cases with relevant disease (PMID: 31408864, Sanchez_2018_(no PMID; abstract)). Functional assessments of this variant are not available in the literature. E1570K has been observed in population frequency databases (gnomAD: SAS 0.02%). In summary, there is insufficient evidence to classify NM_000092.4(COL4A4):c.4708G>A(E1570K) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 25, 2025

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