NM_001001557.4(GDF6):c.209G>A (p.Arg70Gln) AND multiple conditions

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 26, 2023
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:: RCV003083293.3

Allele description

NM_001001557.4(GDF6):c.209G>A (p.Arg70Gln)

Gene:

GDF6:growth differentiation factor 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q22.1

Genomic location:

Preferred name:

NM_001001557.4(GDF6):c.209G>A (p.Arg70Gln)

HGVS:

NC_000008.11:g.96160484C>T
NG_008981.1:g.5309G>A
NM_001001557.4:c.209G>AMANE SELECT
NP_001001557.1:p.Arg70Gln
NC_000008.10:g.97172712C>T

Protein change:

R70Q

Molecular consequence:

NM_001001557.4:c.209G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Klippel-Feil syndrome 1, autosomal dominant (KFS1)
Synonyms:: CERVICAL VERTEBRAL FUSION, AUTOSOMAL DOMINANT
Identifiers:: MONDO: MONDO:0007306; MedGen: C1861689; Orphanet: 2345; OMIM: 118100

Name:: Isolated microphthalmia 4
Identifiers:: MONDO: MONDO:0013130; MedGen: C2751307; Orphanet: 2542; OMIM: 613094

Name:: Microphthalmia, isolated, with coloboma 6 (MCOPCB6)
Synonyms:: Microphthalmia with coloboma 6, digenic; Microphthalmia with coloboma 6; MICROPHTHALMIA/COLOBOMA 6
Identifiers:: MONDO: MONDO:0013376; MedGen: C3150968; Orphanet: 98938; OMIM: 613703

Name:: Leber congenital amaurosis 17 (LCA17)
Identifiers:: MONDO: MONDO:0014145; MedGen: C3715164; Orphanet: 65; OMIM: 615360

Recent activity

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PREDICTED: Homo sapiens RHEB like 1 (RHEBL1), transcript variant X1, mRNA
PREDICTED: Homo sapiens RHEB like 1 (RHEBL1), transcript variant X1, mRNA
gi|2217287409|ref|XM_047428284.1|

Nucleotide
Chain B, Crystal structure of a POU/HMG/DNA ternary complex
Chain B, Crystal structure of a POU/HMG/DNA ternary complex
gi|28373289|pdb|1GT0|B

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003457238	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 26, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003457238

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 26, 2023)

germline

clinical testing

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

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 Invitae, SCV003457238.2

#	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 arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 70 of the GDF6 protein (p.Arg70Gln). This variant is present in population databases (rs563637313, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with GDF6-related conditions. ClinVar contains an entry for this variant (Variation ID: 2149929). 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

Last Updated: Jun 23, 2024

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