Genetic Variant RECQL5:p.Asn917Thr (chr17-75628273-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004259.7(RECQL5):c.2750A>C(p.Asn917Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,614,090 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 8 hom. )

Consequence

RECQL5
NM_004259.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.46

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]

RECQL5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008472115).

BP6

Variant 17-75628273-T-G is Benign according to our data. Variant chr17-75628273-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 715821.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL5	NM_004259.7 link	c.2750A>C	p.Asn917Thr	missense_variant	Exon 18 of 20	ENST00000317905.10	NP_004250.4	O94762-1A0A024R8M9Q8WYH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL5	ENST00000317905.10 link	c.2750A>C	p.Asn917Thr	missense_variant	Exon 18 of 20	1	NM_004259.7	ENSP00000317636.5		O94762-1
RECQL5	ENST00000423245.6 link	c.2669A>C	p.Asn890Thr	missense_variant	Exon 18 of 20	1		ENSP00000394820.2		O94762-4

Frequencies

GnomAD3 genomes

AF:

0.00231

AC:

352

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00340

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00387

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00246

AC:

614

AN:

249480

Hom.:

AF XY:

0.00261

AC XY:

354

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00190

Gnomad FIN exome

AF:

0.00445

Gnomad NFE exome

AF:

0.00339

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00306

AC:

4468

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

2202

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00125

Gnomad4 ASJ exome

AF:

0.00279

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00202

Gnomad4 FIN exome

AF:

0.00448

Gnomad4 NFE exome

AF:

0.00335

Gnomad4 OTH exome

AF:

0.00281

GnomAD4 genome

AF:

0.00231

AC:

352

AN:

152234

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

181

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00340

Gnomad4 NFE

AF:

0.00387

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00328

Hom.:

Bravo

AF:

0.00209

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000487

AC:

ESP6500EA

AF:

0.00322

AC:

ExAC

AF:

0.00291

AC:

352

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00382

EpiControl

AF:

0.00326

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RECQL5-related disorder

Benign:1

Feb 28, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.24

.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.0085

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

.;M

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.4

.;N

REVEL

Benign

0.063

Sift

Uncertain

0.014

.;D

Sift4G

Uncertain

0.022

D;D

Polyphen

0.020

.;B

Vest4

0.38

MVP

0.53

MPC

0.13

ClinPred

0.013

GERP RS

0.63

Varity_R

0.091

gMVP

0.064

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over