NM_004260.4(RECQL4):c.1885C>T (p.Arg629Trp) AND Baller-Gerold syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 23, 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:: RCV000685813.4

Allele description [Variation Report for NM_004260.4(RECQL4):c.1885C>T (p.Arg629Trp)]

NM_004260.4(RECQL4):c.1885C>T (p.Arg629Trp)

Gene:

RECQL4:RecQ like helicase 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q24.3

Genomic location:

Preferred name:

NM_004260.4(RECQL4):c.1885C>T (p.Arg629Trp)

HGVS:

NC_000008.11:g.144514101G>A
NG_016430.2:g.8726C>T
NG_033083.1:g.1137G>A
NM_004260.4:c.1885C>TMANE SELECT
NP_004251.3:p.Arg629Trp
NP_004251.4:p.Arg629Trp
LRG_277t1:c.1885C>T
LRG_277:g.8726C>T
LRG_277p1:p.Arg629Trp
NC_000008.10:g.145739485G>A
NG_016430.1:g.8726C>T
NM_004260.3:c.1885C>T

Protein change:

R629W

Links:

dbSNP: rs772074149

NCBI 1000 Genomes Browser:

rs772074149

Molecular consequence:

NM_004260.4:c.1885C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Baller-Gerold syndrome (BGS)
Synonyms:: Craniosynostosis radial aplasia syndrome; Craniosynostosis with radial defects
Identifiers:: MONDO: MONDO:0009039; MedGen: C0265308; Orphanet: 1225; OMIM: 218600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000813311	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 23, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33144682, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000813311

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 23, 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

Impact of integrated translational research on clinical exome sequencing.

Klee EW, Cousin MA, Pinto E Vairo F, Morales-Rosado JA, Macke EL, Jenkinson WG, Ferrer A, Schultz-Rogers LE, Olson RJ, Oliver GR, Sigafoos AN, Schwab TL, Zimmermann MT, Urrutia RA, Kaiwar C, Gupta A, Blackburn PR, Boczek NJ, Prochnow CA, Lowy RJ, Mulvihill LA, McAllister TM, et al.

Genet Med. 2021 Mar;23(3):498-507. doi: 10.1038/s41436-020-01005-9. Epub 2020 Nov 4. Erratum in: Genet Med. 2023 Feb;25(2):100359.

PubMed [citation]

PMID:: 33144682

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000813311.4

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

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 629 of the RECQL4 protein (p.Arg629Trp). This variant is present in population databases (rs772074149, gnomAD 0.04%). This missense change has been observed in individual(s) with an unspecified neurological disease (PMID: 33144682). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 450513). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RECQL4 protein function. 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: Aug 5, 2023

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