rs368611522
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_004260.4(RECQL4):c.2467G>A(p.Glu823Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,555,340 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign 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. E823G) has been classified as Uncertain significance.
Frequency
Consequence
NM_004260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2467G>A | p.Glu823Lys | missense_variant | 15/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2467G>A | p.Glu823Lys | missense_variant | 15/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.1396G>A | p.Glu466Lys | missense_variant | 14/20 | 1 | |||
ENST00000580385.1 | n.271+298C>T | intron_variant, non_coding_transcript_variant | 3 | ||||||
RECQL4 | ENST00000534626.6 | c.640G>A | p.Glu214Lys | missense_variant | 6/8 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 22AN: 146134Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000213 AC: 43AN: 201436Hom.: 1 AF XY: 0.000202 AC XY: 22AN XY: 108886
GnomAD4 exome AF: 0.000144 AC: 203AN: 1409108Hom.: 2 Cov.: 66 AF XY: 0.000144 AC XY: 100AN XY: 694024
GnomAD4 genome ? AF: 0.000150 AC: 22AN: 146232Hom.: 0 Cov.: 34 AF XY: 0.000156 AC XY: 11AN XY: 70694
ClinVar
Submissions by phenotype
not specified Uncertain:1Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 09, 2021 | DNA sequence analysis of the RECQL4 gene demonstrated a sequence change, c.2467G>A, in exon 15 that results in an amino acid change, p.Glu823Lys. This sequence change has been described in the gnomAD database with a frequency of 0.25% in the Ashkenazi Jewish subpopulation (dbSNP rs368611522). The p.Glu823Lys change affects a moderately conserved amino acid residue located in a domain of the RECQL4 protein that is not known to be functional. The p.Glu823Lys substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD). This sequence change does not appear to have been previously described in individuals with RECQL4-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Glu823Lys change remains unknown at this time. - |
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
RECQL4-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 24, 2023 | The RECQL4 c.2467G>A variant is predicted to result in the amino acid substitution p.Glu823Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.25% of alleles in individuals of Ashkenazi Jewish descent in gnomAD, including one homozygote. This variant is listed in ClinVar with conflicting interpretations of uncertain, likely benign and benign (https://www.ncbi.nlm.nih.gov/clinvar/variation/135141/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Baller-Gerold syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jun 23, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at