chr8-144513628-G-A
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3
The NM_004260.4(RECQL4):c.2143C>T(p.Arg715Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,599,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R715Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_004260.4 missense
Scores
Clinical Significance
Conservation
Publications
- Baller-Gerold syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet
- Rothmund-Thomson syndromeInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- Rothmund-Thomson syndrome type 2Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
- osteosarcomaInheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
- rapadilino syndromeInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
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ACMG classification
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152228Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000808 AC: 18AN: 222760 AF XY: 0.0000991 show subpopulations
GnomAD4 exome AF: 0.000102 AC: 147AN: 1447610Hom.: 0 Cov.: 47 AF XY: 0.000114 AC XY: 82AN XY: 718884 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000105 AC: 16AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74358 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Uncertain:2
RECQL4: PM2 -
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Baller-Gerold syndrome Uncertain:1
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 715 of the RECQL4 protein (p.Arg715Trp). This variant is present in population databases (rs373292946, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. ClinVar contains an entry for this variant (Variation ID: 407017). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt RECQL4 protein function with a positive predictive value of 80%. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at