12-21470205-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_002907.4(RECQL):c.1939G>A(p.Asp647Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,611,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002907.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RECQL | ENST00000444129.7 | c.1939G>A | p.Asp647Asn | missense_variant | Exon 15 of 15 | 2 | NM_002907.4 | ENSP00000416739.2 | ||
RECQL | ENST00000421138.6 | c.1939G>A | p.Asp647Asn | missense_variant | Exon 16 of 16 | 1 | ENSP00000395449.2 | |||
PYROXD1 | ENST00000240651.14 | c.*1451C>T | 3_prime_UTR_variant | Exon 12 of 12 | 1 | NM_024854.5 | ENSP00000240651.9 | |||
PYROXD1 | ENST00000538582.5 | c.*1451C>T | 3_prime_UTR_variant | Exon 12 of 12 | 2 | ENSP00000438505.1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151790Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 250076Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135172
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1459732Hom.: 0 Cov.: 37 AF XY: 0.0000358 AC XY: 26AN XY: 726176
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151790Hom.: 0 Cov.: 29 AF XY: 0.0000270 AC XY: 2AN XY: 74136
ClinVar
Submissions by phenotype
not provided Uncertain:2
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 647 of the RECQL protein (p.Asp647Asn). This variant is present in population databases (rs762901544, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RECQL-related conditions. ClinVar contains an entry for this variant (Variation ID: 1011683). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. -
The frequency of this variant in the general population, 0.000008 (2/250076 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant was found both in individuals with breast cancer as well as unaffected individuals in a large breast cancer association study (PMID: 33471991 (2021), see also LOVD (https://databases.lovd.nl/shared/variants/RECQL). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. -
RECON progeroid syndrome Uncertain:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at