17-75630842-G-GTT

Variant names:

• chr17-75630842-G-GTT
• rs56158987
• NM_004259.7:c.1586-6_1586-5insAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004259.7(RECQL5):​c.1586-6_1586-5insAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000261 in 1,147,246 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: RECQL5 NM_004259.7 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• coronary artery disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004259.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL5	NM_004259.7	MANE Select	c.1586-6_1586-5insAA		splice_region intron	N/A	NP_004250.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL5	ENST00000317905.10	TSL:1 MANE Select	c.1586-6_1586-5insAA		splice_region intron	N/A	ENSP00000317636.5
	RECQL5	ENST00000423245.6	TSL:1	c.1505-6_1505-5insAA		splice_region intron	N/A	ENSP00000394820.2
	RECQL5	ENST00000443199.6	TSL:1	n.1122-6_1122-5insAA		splice_region intron	N/A

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000261 AC: 3 AN: 1147246 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 561690

African (AFR) AF: 0.00 AC: 0 AN: 21782

American (AMR) AF: 0.00 AC: 0 AN: 23172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16612

East Asian (EAS) AF: 0.00 AC: 0 AN: 25814

South Asian (SAS) AF: 0.0000343 AC: 2 AN: 58250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4570

European-Non Finnish (NFE) AF: 0.00000110 AC: 1 AN: 912520

Other (OTH) AF: 0.00 AC: 0 AN: 46884

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.26

Splicing

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

Other links and lift over

dbSNP: rs56158987; hg19: chr17-73626922;