rs786200890

Variant names:

• chr8-144514061-GCTGTGA-G
• rs786200890
• NM_004260.4:c.1919_1924delTCACAG

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_004260.4(RECQL4):​c.1919_1924delTCACAG​(p.Leu640_Ala642delinsPro) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: RECQL4 NM_004260.4 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 7.91

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_004260.4.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.1919_1924delTCACAG	p.Leu640_Ala642delinsPro	disruptive_inframe_deletion	Exon 12 of 21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.1919_1924delTCACAG	p.Leu640_Ala642delinsPro	disruptive_inframe_deletion	Exon 12 of 21	1	NM_004260.4	ENSP00000482313.2
RECQL4	ENST00000621189.4	c.848_853delTCACAG	p.Leu283_Ala285delinsPro	disruptive_inframe_deletion	Exon 11 of 20	1		ENSP00000483145.1
RECQL4	ENST00000534626.6	c.287_292delTCACAG	p.Leu96_Ala98delinsPro	disruptive_inframe_deletion	Exon 3 of 8	5		ENSP00000477457.1
RECQL4	ENST00000532846.2	c.773_778delTCACAG	p.Leu258_Ala260delinsPro	disruptive_inframe_deletion	Exon 8 of 9	5		ENSP00000476551.1

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rothmund-Thomson syndrome type 2 Pathogenic:1

Jun 01, 2010

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Baller-Gerold syndrome Uncertain:1

Aug 25, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 6076). This variant has been observed in individual(s) with Rothmund-Thomson syndrome (PMID: 20503338). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This variant, c.1919_1924del, is a complex sequence change that results in the deletion of 2 and insertion of 1 amino acid(s) in the RECQL4 protein (p.Leu640_Ala642delinsPro). -

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: rs786200890; hg19: chr8-145739445;