8-144513027-TGGTGCA-TGGTGCAGGTGCAGGTGCA

Variant names:

• chr8-144513027-T-TGGTGCAGGTGCA
• rs548804317
• NM_004260.4:c.2563_2574dupTGCACCTGCACC

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_004260.4(RECQL4):​c.2563_2574dupTGCACCTGCACC​(p.Thr858_Arg859insCysThrCysThr) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000281 in 1,422,152 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: RECQL4 NM_004260.4 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.833

Genes affected

RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]

ENSG00000265393 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_004260.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.2563_2574dupTGCACCTGCACC	p.Thr858_Arg859insCysThrCysThr	conservative_inframe_insertion	Exon 15 of 21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.2563_2574dupTGCACCTGCACC	p.Thr858_Arg859insCysThrCysThr	conservative_inframe_insertion	Exon 15 of 21	1	NM_004260.4	ENSP00000482313.2
RECQL4	ENST00000621189.4	c.1492_1503dupTGCACCTGCACC	p.Thr501_Arg502insCysThrCysThr	conservative_inframe_insertion	Exon 14 of 20	1		ENSP00000483145.1
RECQL4	ENST00000534626.6	c.733_744dupTGCACCTGCACC	p.Thr248_Arg249insCysThrCysThr	conservative_inframe_insertion	Exon 6 of 8	5		ENSP00000477457.1
ENSG00000265393	ENST00000580385.1	n.271+199_271+210dupTGCAGGTGCAGG		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000281 AC: 4 AN: 1422152 Hom.: 0 Cov.: 66 AF XY: 0.00000142 AC XY: 1 AN XY: 703988

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000535

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.15e-7

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Baller-Gerold syndrome Uncertain:1

Apr 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.2563_2574dup, results in the insertion of 4 amino acid(s) of the RECQL4 protein (p.Cys855_Thr858dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. ClinVar contains an entry for this variant (Variation ID: 846095). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

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: rs548804317; hg19: chr8-145738410;