NM_000557.5(GDF5):c.1313_1314delinsTT (p.Arg438Leu) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 1, 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:: RCV001992913.3

Allele description [Variation Report for NM_000557.5(GDF5):c.1313_1314delinsTT (p.Arg438Leu)]

NM_000557.5(GDF5):c.1313_1314delinsTT (p.Arg438Leu)

Genes:

GDF5-AS1:GDF5 antisense RNA 1 [Gene - HGNC]
GDF5:growth differentiation factor 5 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

20q11.22

Genomic location:

Preferred name:

NM_000557.5(GDF5):c.1313_1314delinsTT (p.Arg438Leu)

HGVS:

NC_000020.11:g.35434101_35434102delinsAA
NG_008076.3:g.25645_25646delinsTT
NM_000557.5:c.1313_1314delinsTTMANE SELECT
NM_001319138.2:c.1313_1314delinsTT
NP_000548.2:p.Arg438Leu
NP_001306067.1:p.Arg438Leu
NC_000020.10:g.34021899_34021900delinsAA
NR_161326.1:n.385_386delinsAA

Protein change:

R438L

Links:

dbSNP: rs2146578516

NCBI 1000 Genomes Browser:

rs2146578516

Molecular consequence:

NM_000557.5:c.1313_1314delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001319138.2:c.1313_1314delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NR_161326.1:n.385_386delinsAA - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Taxonomy Links for GEO Profiles (Select 7335545) (1)
Taxonomy

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002234545	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 1, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16127465, 16532400, 28032038, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002234545

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 1, 2022)

germline

clinical testing

PubMed (4)
[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

Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2.

Seemann P, Schwappacher R, Kjaer KW, Krakow D, Lehmann K, Dawson K, Stricker S, Pohl J, Plöger F, Staub E, Nickel J, Sebald W, Knaus P, Mundlos S.

J Clin Invest. 2005 Sep;115(9):2373-81. Epub 2005 Aug 25.

PubMed [citation]

PMID:: 16127465
PMCID:: PMC1190374

GDF5 is a second locus for multiple-synostosis syndrome.

Dawson K, Seeman P, Sebald E, King L, Edwards M, Williams J 3rd, Mundlos S, Krakow D.

Am J Hum Genet. 2006 Apr;78(4):708-12. Epub 2006 Feb 24.

PubMed [citation]

PMID:: 16532400
PMCID:: PMC1424701

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002234545.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GDF5 function (PMID: 16127465). 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: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 1450722). This missense change has been observed in individuals with symphalangism (PMID: 16127465, 16532400, 28032038). It has also been observed to segregate with disease in related individuals. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces arginine with leucine at codon 438 of the GDF5 protein (p.Arg438Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine.

#	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 28, 2024

ClinVar

Relating variation to medicine