rs1389647533
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_004260.4(RECQL4):c.871del(p.Ala291LeufsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,612,626 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
RECQL4
NM_004260.4 frameshift
NM_004260.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.00800
Genes affected
RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
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Very rare variant in population databases, with high coverage;
PP5
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Variant 8-144516247-GC-G is Pathogenic according to our data. Variant chr8-144516247-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 459525.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.871del | p.Ala291LeufsTer2 | frameshift_variant | 5/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.871del | p.Ala291LeufsTer2 | frameshift_variant | 5/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.-201del | 5_prime_UTR_variant | 4/20 | 1 | ||||
RECQL4 | ENST00000524998.1 | c.393del | p.Ala132LeufsTer2 | frameshift_variant | 3/4 | 3 | |||
RECQL4 | ENST00000534538.1 | c.*675del | 3_prime_UTR_variant, NMD_transcript_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152178Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00000405 AC: 1AN: 246922Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134592
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1460448Hom.: 0 Cov.: 66 AF XY: 0.0000193 AC XY: 14AN XY: 726468
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152178Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74344
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Baller-Gerold syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2023 | This sequence change creates a premature translational stop signal (p.Ala291Leufs*2) in the RECQL4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RECQL4 are known to be pathogenic (PMID: 12734318, 12952869). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 459525). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at