chr17-75627694-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP3
The NM_004259.7(RECQL5):c.2806-2A>G variant causes a splice acceptor change. The variant allele was found at a frequency of 0.000579 in 1,602,070 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00060 ( 1 hom. )
Consequence
RECQL5
NM_004259.7 splice_acceptor
NM_004259.7 splice_acceptor
Scores
2
3
2
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 4.50
Genes affected
RECQL5 (HGNC:9950): (RecQ like helicase 5) The protein encoded by this gene is a helicase that is important for genome stability. The encoded protein also prevents aberrant homologous recombination by displacing RAD51 from ssDNA. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.023185484 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.9, offset of 48, new splice context is: tctcacacttgctgactcAGaag. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP3
Multiple lines of computational evidence support a deleterious effect 5: Cadd, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai, Eigen [when BayesDel_addAF, MutationTaster was below the threshold]
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL5 | NM_004259.7 | c.2806-2A>G | splice_acceptor_variant | ENST00000317905.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL5 | ENST00000317905.10 | c.2806-2A>G | splice_acceptor_variant | 1 | NM_004259.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000408 AC: 62AN: 151934Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000404 AC: 91AN: 225264Hom.: 1 AF XY: 0.000392 AC XY: 48AN XY: 122438
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GnomAD4 exome AF: 0.000597 AC: 866AN: 1450136Hom.: 1 Cov.: 31 AF XY: 0.000547 AC XY: 394AN XY: 720198
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GnomAD4 genome AF: 0.000408 AC: 62AN: 151934Hom.: 0 Cov.: 33 AF XY: 0.000377 AC XY: 28AN XY: 74198
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D;D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at