NM_152732.5(RSPH9):c.386A>G (p.Glu129Gly) AND Primary ciliary dyskinesia

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 8, 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:: RCV002923726.12

Allele description [Variation Report for NM_152732.5(RSPH9):c.386A>G (p.Glu129Gly)]

NM_152732.5(RSPH9):c.386A>G (p.Glu129Gly)

Gene:

RSPH9:radial spoke head component 9 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.1

Genomic location:

Preferred name:

NM_152732.5(RSPH9):c.386A>G (p.Glu129Gly)

HGVS:

NC_000006.12:g.43650533A>G
NG_023436.1:g.10504A>G
NG_028283.4:g.138446A>G
NM_001193341.2:c.386A>G
NM_001424119.1:c.386A>G
NM_001424120.1:c.386A>G
NM_001424121.1:c.386A>G
NM_152732.5:c.386A>GMANE SELECT
NP_001180270.1:p.Glu129Gly
NP_001411048.1:p.Glu129Gly
NP_001411049.1:p.Glu129Gly
NP_001411050.1:p.Glu129Gly
NP_689945.2:p.Glu129Gly
NC_000006.11:g.43618270A>G
NM_152732.4:c.386A>G
NR_187614.1:n.449A>G

Protein change:

E129G

Molecular consequence:

NM_001193341.2:c.386A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001424119.1:c.386A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001424120.1:c.386A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001424121.1:c.386A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_152732.5:c.386A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_187614.1:n.449A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Primary ciliary dyskinesia
Synonyms:: Ciliary dyskinesia
Identifiers:: MONDO: MONDO:0016575; MedGen: C0008780; OMIM: PS244400; Human Phenotype Ontology: HP:0012265

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003273976	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 8, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003741221	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 27, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003273976

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 8, 2024)

germline

clinical testing

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

SCV003741221

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 27, 2021)

germline

clinical testing

Citation Link

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003273976.2

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

Description

This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 129 of the RSPH9 protein (p.Glu129Gly). This variant is present in population databases (rs751900140, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RSPH9-related conditions. ClinVar contains an entry for this variant (Variation ID: 2063036). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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.

#	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 Ambry Genetics, SCV003741221.2

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

Description

The c.386A>G (p.E129G) alteration is located in exon 2 (coding exon 2) of the RSPH9 gene. This alteration results from a A to G substitution at nucleotide position 386, causing the glutamic acid (E) at amino acid position 129 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

#	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: Nov 10, 2024

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