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GeneBe

17-75627694-T-C

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

Scores

2
3
2
Splicing: ADA: 1.000
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.50
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PVS1
?
    PVS1 - null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease
Splicing variant, 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
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PP3
?
    PP3 - Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.)
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
RECQL5NM_004259.7 linkuse as main transcriptc.2806-2A>G splice_acceptor_variant ENST00000317905.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RECQL5ENST00000317905.10 linkuse as main transcriptc.2806-2A>G splice_acceptor_variant 1 NM_004259.7 P1O94762-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000408
AC:
62
AN:
151934
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00548
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000574
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000404
AC:
91
AN:
225264
Hom.:
1
AF XY:
0.000392
AC XY:
48
AN XY:
122438
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000190
Gnomad ASJ exome
AF:
0.00355
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000103
Gnomad NFE exome
AF:
0.000477
Gnomad OTH exome
AF:
0.000178
GnomAD4 exome
AF:
0.000597
AC:
866
AN:
1450136
Hom.:
1
Cov.:
31
AF XY:
0.000547
AC XY:
394
AN XY:
720198
show subpopulations
Gnomad4 AFR exome
AF:
0.0000899
Gnomad4 AMR exome
AF:
0.000141
Gnomad4 ASJ exome
AF:
0.00390
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000172
Gnomad4 NFE exome
AF:
0.000640
Gnomad4 OTH exome
AF:
0.000650
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000408
AC:
62
AN:
151934
Hom.:
0
Cov.:
33
AF XY:
0.000377
AC XY:
28
AN XY:
74198
show subpopulations
Gnomad4 AFR
AF:
0.0000484
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00548
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000574
Gnomad4 OTH
AF:
0.000956
Alfa
AF:
0.000683
Hom.:
0
Bravo
AF:
0.000416
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000119
AC:
1
ExAC
?
    Exome Aggregation Consortium database
AF:
0.000364
AC:
44

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 submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.025
T
BayesDel_noAF
Uncertain
0.060
Cadd
Pathogenic
28
Dann
Uncertain
0.99
Eigen
Pathogenic
0.82
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Pathogenic
0.98
D
MutationTaster
Benign
1.0
D;D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.93
SpliceAI score (max)
0.94
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.94
Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201841487; hg19: chr17-73623774; COSMIC: COSV58638377; COSMIC: COSV58638377; API