NM_004260.4(RECQL4):c.1036G>T (p.Ala346Ser) AND Baller-Gerold syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 29, 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:: RCV003616273.2

Allele description [Variation Report for NM_004260.4(RECQL4):c.1036G>T (p.Ala346Ser)]

NM_004260.4(RECQL4):c.1036G>T (p.Ala346Ser)

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.1036G>T (p.Ala346Ser)

HGVS:

NC_000008.11:g.144516083C>A
NG_016430.2:g.6744G>T
NG_033083.1:g.3119C>A
NG_033083.2:g.3093C>A
NM_001413017.1:c.954-14G>T
NM_001413018.1:c.1036G>T
NM_001413019.1:c.1036G>T
NM_001413020.1:c.954-14G>T
NM_001413021.1:c.-36G>T
NM_001413022.1:c.-36G>T
NM_001413023.1:c.-36G>T
NM_001413024.1:c.-36G>T
NM_001413025.1:c.907G>T
NM_001413027.1:c.-98G>T
NM_001413028.1:c.-36G>T
NM_001413029.1:c.685G>T
NM_001413030.1:c.-98G>T
NM_001413031.1:c.-98G>T
NM_001413032.1:c.-98G>T
NM_001413033.1:c.1036G>T
NM_001413034.1:c.-22-14G>T
NM_001413035.1:c.-36G>T
NM_001413036.1:c.1036G>T
NM_001413037.1:c.-36G>T
NM_001413038.1:c.-36G>T
NM_001413039.1:c.1036G>T
NM_001413040.1:c.-36G>T
NM_001413041.1:c.-98G>T
NM_001413042.1:c.-36G>T
NM_001413043.1:c.-305G>T
NM_004260.4:c.1036G>TMANE SELECT
NP_001399947.1:p.Ala346Ser
NP_001399948.1:p.Ala346Ser
NP_001399954.1:p.Ala303Ser
NP_001399958.1:p.Ala229Ser
NP_001399962.1:p.Ala346Ser
NP_001399965.1:p.Ala346Ser
NP_001399968.1:p.Ala346Ser
NP_004251.4:p.Ala346Ser
LRG_277t1:c.1036G>T
LRG_277:g.6744G>T
LRG_277p1:p.Ala346Ser
NC_000008.10:g.145741467C>A
NR_182090.1:n.1085G>T
NR_182091.1:n.1085G>T
NR_182092.1:n.1085G>T

Protein change:

A229S

Molecular consequence:

NM_001413021.1:c.-36G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413022.1:c.-36G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413023.1:c.-36G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413024.1:c.-36G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413027.1:c.-98G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413028.1:c.-36G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413030.1:c.-98G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413031.1:c.-98G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413032.1:c.-98G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413035.1:c.-36G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413037.1:c.-36G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413038.1:c.-36G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413040.1:c.-36G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413041.1:c.-98G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413042.1:c.-36G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413043.1:c.-305G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001413017.1:c.954-14G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001413020.1:c.954-14G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001413034.1:c.-22-14G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001413018.1:c.1036G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001413019.1:c.1036G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001413025.1:c.907G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001413029.1:c.685G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001413033.1:c.1036G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001413036.1:c.1036G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001413039.1:c.1036G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004260.4:c.1036G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_182090.1:n.1085G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_182091.1:n.1085G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_182092.1:n.1085G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV004408911	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 29, 2022)	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

SCV004408911

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 29, 2022)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004408911.1

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

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 346 of the RECQL4 protein (p.Ala346Ser). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 not expected to disrupt RECQL4 protein function.

#	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: Sep 29, 2024

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