17-75630842-G-GTGTGT

Variant names:

• chr17-75630842-G-GTGTGT
• rs56158987
• NM_004259.7:c.1586-6_1586-5insACACA

Variant summary

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

The NM_004259.7(RECQL5):​c.1586-6_1586-5insACACA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000061 in 1,147,244 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000061 (1 hom.)
• Consequence: RECQL5 NM_004259.7 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• Publications: 7 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 0 ACMG points.

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_1586-5insACACA		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_1586-5insACACA		splice_region intron	N/A	ENSP00000317636.5
	RECQL5	ENST00000423245.6	TSL:1	c.1505-6_1505-5insACACA		splice_region intron	N/A	ENSP00000394820.2
	RECQL5	ENST00000443199.6	TSL:1	n.1122-6_1122-5insACACA		splice_region intron	N/A

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.0000348 AC: 2 AN: 57474 AF XY: 0.0000691

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000861

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000610 AC: 7 AN: 1147244 Hom.: 1 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 561690

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

American (AMR) AF: 0.0000863 AC: 2 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: 0.00 AC: 0 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: 0.00000438 AC: 4 AN: 912518

Other (OTH) AF: 0.0000213 AC: 1 AN: 46884

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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;