17-75630842-G-GTGT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_004259.7(RECQL5):c.1586-6_1586-5insACA variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 1,139,402 control chromosomes in the GnomAD database, including 1,959 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (269 hom., cov: 21)
  • Exomes 𝑓: 0.063 (1959 hom.)
  • Failed GnomAD Quality Control
• Consequence: RECQL5 NM_004259.7 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.258

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.

• BP6: Variant 17-75630842-G-GTGT is Benign according to our data. Variant chr17-75630842-G-GTGT is described in ClinVar as [Benign]. Clinvar id is 403370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL5	NM_004259.7	c.1586-6_1586-5insACA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000317905.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL5	ENST00000317905.10	c.1586-6_1586-5insACA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004259.7	P1
RECQL5	ENST00000423245.6	c.1505-6_1505-5insACA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
RECQL5	ENST00000443199.6	n.1122-6_1122-5insACA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
RECQL5	ENST00000580707.1	c.53-6_53-5insACA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 6424 AN: 108212 Hom.: 269 Cov.: 21 FAILED QC

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0391

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.00480

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.0622

Gnomad MID AF: 0.0690

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.0531

GnomAD3 exomes AF: 0.124 AC: 7134 AN: 57474 Hom.: 1182 AF XY: 0.122 AC XY: 3536 AN XY: 28946

Gnomad AFR exome AF: 0.0323

Gnomad AMR exome AF: 0.0790

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.0570

Gnomad SAS exome AF: 0.104

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.0631 AC: 71928 AN: 1139402 Hom.: 1959 Cov.: 25 AF XY: 0.0628 AC XY: 35040 AN XY: 557830

Gnomad4 AFR exome AF: 0.0135

Gnomad4 AMR exome AF: 0.0320

Gnomad4 ASJ exome AF: 0.0395

Gnomad4 EAS exome AF: 0.00380

Gnomad4 SAS exome AF: 0.0370

Gnomad4 FIN exome AF: 0.0668

Gnomad4 NFE exome AF: 0.0694

Gnomad4 OTH exome AF: 0.0543

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0593 AC: 6423 AN: 108248 Hom.: 269 Cov.: 21 AF XY: 0.0560 AC XY: 2916 AN XY: 52056

Gnomad4 AFR AF: 0.0202

Gnomad4 AMR AF: 0.0390

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.00456

Gnomad4 SAS AF: 0.0338

Gnomad4 FIN AF: 0.0622

Gnomad4 NFE AF: 0.0835

Gnomad4 OTH AF: 0.0530

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

RECQL5-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 04, 2019

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

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56158987; hg19: chr17-73626922;