NM_000406.3(GNRHR):c.785G>A (p.Arg262Gln) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 11, 2019
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:: RCV000494391.1

Allele description

NM_000406.3(GNRHR):c.785G>A (p.Arg262Gln)

Gene:

GNRHR:gonadotropin releasing hormone receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q13.2

Genomic location:

Preferred name:

NM_000406.3(GNRHR):c.785G>A (p.Arg262Gln)

HGVS:

NC_000004.12:g.67740682C>T
NG_009293.1:g.20405G>A
NM_000406.3:c.785G>AMANE SELECT
NM_001012763.2:c.657G>A
NP_000397.1:p.Arg262Gln
NP_000397.1:p.Arg262Gln
NP_001012781.1:p.Thr219=
NC_000004.11:g.68606400C>T
NM_000406.2:c.785G>A
P30968:p.Arg262Gln

Protein change:

R262Q; ARG262GLN

Links:

UniProtKB: P30968#VAR_019319; OMIM: 138850.0002; dbSNP: rs104893837

NCBI 1000 Genomes Browser:

rs104893837

Molecular consequence:

NM_000406.3:c.785G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001012763.2:c.657G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000583021	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jan 11, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000583021

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jan 11, 2019)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000583021.3

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

Description

The R262Q variant has been published previously as a pathogenic founder variant in association with GNRHR-related disorders (de Roux et al., 1997; Lin et al., 2006; Pitteloud et al., 2007). The R262Q variant is observed in 36/6614 (0.544%) alleles from individuals of Finnish background in the ExAC dataset (Lek et al., 2016). R262Q is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Functional studies have shown R262Q impairs IP3 production and GnRH signal transmission (de Roux et al., 1997; Layman et al., 1998). In summary, we consider this variant to be pathogenic.

#	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

Last Updated: Aug 21, 2021

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