Genetic Variant RECQL:c.1355+103G>A (chr12-21474738-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002907.4(RECQL):c.1355+103G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000103 in 967,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

RECQL
NM_002907.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0360

Publications

0 publications found

Variant links:

Genes affected

RECQL (HGNC:9948): (RecQ like helicase) The protein encoded by this gene is a member of the RecQ DNA helicase family. DNA helicases are enzymes involved in various types of DNA repair, including mismatch repair, nucleotide excision repair and direct repair. The encoded protein is involved in the processing of Holliday junctions, the suppression of sister chromatid exchanges, telomere maintenance, and is required for genotoxic stress resistance. Defects in this gene have been associated with several types of cancer. [provided by RefSeq, Jan 2017]

RECQL Gene-Disease associations (from GenCC):

RECON progeroid syndrome
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
breast cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

RECQL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002907.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL	NM_002907.4	MANE Select	c.1355+103G>A		intron	N/A	NP_002898.2
	RECQL	NM_032941.3		c.1355+103G>A		intron	N/A	NP_116559.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL	ENST00000444129.7	TSL:2 MANE Select	c.1355+103G>A		intron	N/A	ENSP00000416739.2
	RECQL	ENST00000421138.6	TSL:1	c.1355+103G>A		intron	N/A	ENSP00000395449.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000103

AC:

AN:

967094

Hom.:

AF XY:

0.00

AC XY:

AN XY:

493000

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

23964

American (AMR)

AF:

0.00

AC:

AN:

36700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19774

East Asian (EAS)

AF:

0.00

AC:

AN:

36788

South Asian (SAS)

AF:

0.00

AC:

AN:

65386

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3272

European-Non Finnish (NFE)

AF:

0.00000145

AC:

AN:

691922

Other (OTH)

AF:

0.00

AC:

AN:

43362

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.6

(source)

DANN

Benign

0.48

PhyloP100

0.036

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over