17-75628273-T-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.46

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]

ACMG classification

Verdict is Benign. Variant got -16 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_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL5	NM_004259.7	c.2750A>C	p.Asn917Thr	missense_variant	18/20	ENST00000317905.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL5	ENST00000317905.10	c.2750A>C	p.Asn917Thr	missense_variant	18/20	1	NM_004259.7	P1

Frequencies

GnomAD3 genomes AF: 0.00231 AC: 352 AN: 152116 Hom.: 3 Cov.: 32

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.: 0 AF XY: 0.00261 AC XY: 354 AN XY: 135380

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.: 8 Cov.: 32 AF XY: 0.00303 AC XY: 2202 AN XY: 727226

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.: 3 Cov.: 32 AF XY: 0.00243 AC XY: 181 AN XY: 74430

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.: 2

Bravo AF: 0.00209

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000487 AC: 2

ESP6500EA AF: 0.00322 AC: 27

ExAC AF: 0.00291 AC: 352

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00382

EpiControl AF: 0.00326

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

RECQL5-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2022

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

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	14
Dann	Benign	0.77
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.0085	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.22	T
REVEL	Benign	0.063
Sift4G	Uncertain	0.022	D;D
Polyphen		0.020	.;B
Vest4		0.38
MVP		0.53
MPC		0.13
ClinPred		0.013	T
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

Other links and lift over

dbSNP: rs140565320; hg19: chr17-73624353; COSMIC: COSV58641185; COSMIC: COSV58641185;