rs11342077

Positions:

• chr8-144513384-C-CG

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_004260.4(RECQL4):​c.2296_2297insC​(p.Arg766ProfsTer43) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RECQL4 NM_004260.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

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]

(HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.2296_2297insC	p.Arg766ProfsTer43	frameshift_variant	14/21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.2296_2297insC	p.Arg766ProfsTer43	frameshift_variant	14/21	1	NM_004260.4	ENSP00000482313	P1
RECQL4	ENST00000621189.4	c.1225_1226insC	p.Arg409ProfsTer43	frameshift_variant	13/20	1		ENSP00000483145
	ENST00000580385.1	n.272-221dup		intron_variant, non_coding_transcript_variant		3
RECQL4	ENST00000534626.6	c.634+31_634+32insC		intron_variant		5		ENSP00000477457

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000212 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11342077; hg19: chr8-145738767;