rs754324912
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004260.4(RECQL4):c.2492A>G(p.His831Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000755 in 1,562,896 control chromosomes in the GnomAD database, including 1 homozygotes. 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. H831Y) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2492A>G | p.His831Arg | missense_variant | 15/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2492A>G | p.His831Arg | missense_variant | 15/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.1421A>G | p.His474Arg | missense_variant | 14/20 | 1 | |||
ENST00000580385.1 | n.271+273T>C | intron_variant, non_coding_transcript_variant | 3 | ||||||
RECQL4 | ENST00000534626.6 | c.665A>G | p.His222Arg | missense_variant | 6/8 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000739 AC: 11AN: 148770Hom.: 1 Cov.: 34
GnomAD3 exomes AF: 0.0000714 AC: 15AN: 210102Hom.: 0 AF XY: 0.0000791 AC XY: 9AN XY: 113746
GnomAD4 exome AF: 0.0000757 AC: 107AN: 1414126Hom.: 0 Cov.: 66 AF XY: 0.0000831 AC XY: 58AN XY: 697848
GnomAD4 genome ? AF: 0.0000739 AC: 11AN: 148770Hom.: 1 Cov.: 34 AF XY: 0.000124 AC XY: 9AN XY: 72444
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Rothmund-Thomson syndrome type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 13, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 831 of the RECQL4 protein (p.His831Arg). This variant is present in population databases (rs754324912, 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: 239734). 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 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