Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM1BP4_StrongBP6_Very_StrongBS2
The NM_004260.4(RECQL4):c.1576C>T(p.Leu526Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000404 in 1,611,946 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
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]
PM1 - Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 16 uncertain in NM_004260.4
BP4
?
BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.010399044).
BP6
?
BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-144514980-G-A is Benign according to our data. Variant chr8-144514980-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 135174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age