Genetic Variant RECQL5:p.Val880Ile (chr17-75628385-C-T) – 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.2638G>A(p.Val880Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,613,998 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 4 hom. )

Consequence

RECQL5
NM_004259.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.03

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=0.0053915977).

BP6

Variant 17-75628385-C-T is Benign according to our data. Variant chr17-75628385-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2648275.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL5	NM_004259.7 link	c.2638G>A	p.Val880Ile	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.2638G>A	p.Val880Ile	missense_variant	Exon 18 of 20	1	NM_004259.7	ENSP00000317636.5		O94762-1
RECQL5	ENST00000423245.6 link	c.2557G>A	p.Val853Ile	missense_variant	Exon 18 of 20	1		ENSP00000394820.2		O94762-4

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000422

AC:

105

AN:

248856

Hom.:

AF XY:

0.000511

AC XY:

AN XY:

135132

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00324

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000202

AC:

295

AN:

1461692

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

205

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00286

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000105

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000125

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.000241

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000463

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RECQL5-related disorder

Benign:1

Mar 21, 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 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RECQL5: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.033

DANN

Benign

0.81

DEOGEN2

Benign

0.10

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.30

T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.13

.;N

REVEL

Benign

0.010

Sift

Benign

0.15

.;T

Sift4G

Benign

0.30

T;T

Polyphen

0.0

.;B

Vest4

0.13

MVP

0.18

MPC

0.093

ClinPred

0.0075

GERP RS

-1.8

Varity_R

0.028

gMVP

0.044

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