17-75630842-G-GTGTGT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004259.7(RECQL5):c.1586-6_1586-5insACACA 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 0.0000061 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, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD3 exomes AF: 0.0000348 AC: 2 AN: 57474 Hom.: 0 AF XY: 0.0000691 AC XY: 2 AN XY: 28946

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000863

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000438

Gnomad4 OTH exome AF: 0.0000213

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

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;