8-144514050-GTGTGGC-GTGTGGCTGTGGC

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_004260.4(RECQL4):​c.1930_1935dupGCCACA​(p.Thr645_Arg646insAlaThr) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000769 in 1,430,902 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: 0.0000077 ( 0 hom. )

Consequence

RECQL4
NM_004260.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.992
Variant links:
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]

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ACMG classification

Classification made for transcript

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/exons MANE Protein UniProt
RECQL4NM_004260.4 linkc.1930_1935dupGCCACA p.Thr645_Arg646insAlaThr conservative_inframe_insertion 12/21 ENST00000617875.6 NP_004251.4 O94761

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RECQL4ENST00000617875.6 linkc.1930_1935dupGCCACA p.Thr645_Arg646insAlaThr conservative_inframe_insertion 12/211 NM_004260.4 ENSP00000482313.2 O94761
RECQL4ENST00000621189.4 linkc.859_864dupGCCACA p.Thr288_Arg289insAlaThr conservative_inframe_insertion 11/201 ENSP00000483145.1 A0A087X072
RECQL4ENST00000534626.6 linkc.298_303dupGCCACA p.Thr101_Arg102insAlaThr conservative_inframe_insertion 3/85 ENSP00000477457.1 V9GZ64
RECQL4ENST00000532846.2 linkc.784_789dupGCCACA p.Thr263_Arg264insAlaThr conservative_inframe_insertion 8/95 ENSP00000476551.1 V9GYA3

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000769
AC:
11
AN:
1430902
Hom.:
0
Cov.:
36
AF XY:
0.00000846
AC XY:
6
AN XY:
709276
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000265
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000820
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
Cov.:
34
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 26, 2022Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has been observed in individual(s) with Rothmund-Thomson syndrome (PMID: 27247962). This variant is not present in population databases (gnomAD no frequency). This variant, c.1930_1935dup, is a complex sequence change that results in the insertion of 2 amino acid(s) in the RECQL4 protein (p.Ala644_Thr645dup). 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

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs781471399; hg19: chr8-145739434; API