rs774274636
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_004260.4(RECQL4):āc.2780T>Gā(p.Leu927Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,752 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L927P) has been classified as Uncertain significance.
Frequency
Consequence
NM_004260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2780T>G | p.Leu927Arg | missense_variant | 16/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2780T>G | p.Leu927Arg | missense_variant | 16/21 | 1 | NM_004260.4 | P1 | |
ENST00000580385.1 | n.181A>C | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246440Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134430
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1459752Hom.: 0 Cov.: 66 AF XY: 0.00000551 AC XY: 4AN XY: 726170
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Rothmund-Thomson syndrome type 2 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Department of Pediatrics, Memorial Sloan Kettering Cancer Center | Dec 15, 2020 | - - |
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2023 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 863644). This variant is also known as g.T5007G, p.L926R. This missense change has been observed in individual(s) with clinical features of Rothmund-Thomson syndrome (PMID: 18616953, 34308366). This variant is present in population databases (rs774274636, gnomAD 0.003%). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 927 of the RECQL4 protein (p.Leu927Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at