NM_000186.4(CFH):c.269A>G (p.Asp90Gly) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 13, 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:: RCV002664195.2

Allele description [Variation Report for NM_000186.4(CFH):c.269A>G (p.Asp90Gly)]

NM_000186.4(CFH):c.269A>G (p.Asp90Gly)

Gene:

CFH:complement factor H [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q31.3

Genomic location:

Preferred name:

NM_000186.4(CFH):c.269A>G (p.Asp90Gly)

HGVS:

NC_000001.11:g.196673881A>G
NG_007259.1:g.26871A>G
NM_000186.4:c.269A>GMANE SELECT
NM_001014975.3:c.269A>G
NP_000177.2:p.Asp90Gly
NP_000177.2:p.Asp90Gly
NP_001014975.1:p.Asp90Gly
LRG_47t1:c.269A>G
LRG_47:g.26871A>G
LRG_47p1:p.Asp90Gly
NC_000001.10:g.196643011A>G
NM_000186.3:c.269A>G

Protein change:

D90G

Molecular consequence:

NM_000186.4:c.269A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001014975.3:c.269A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003524008	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24847005, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003524008

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 13, 2022)

germline

clinical testing

PubMed (2)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Whole-exome sequencing identifies rare, functional CFH variants in families with macular degeneration.

Yu Y, Triebwasser MP, Wong EK, Schramm EC, Thomas B, Reynolds R, Mardis ER, Atkinson JP, Daly M, Raychaudhuri S, Kavanagh D, Seddon JM.

Hum Mol Genet. 2014 Oct 1;23(19):5283-93. doi: 10.1093/hmg/ddu226. Epub 2014 May 20.

PubMed [citation]

PMID:: 24847005
PMCID:: PMC4159152

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

Details of each submission

From Invitae, SCV003524008.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with age related macular degeneration (PMID: 24847005). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 90 of the CFH protein (p.Asp90Gly).

#	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: Feb 14, 2024

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