rs372372052

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_004260.4(RECQL4):c.2434G>A(p.Ala812Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000146 in 1,586,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A812A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

RECQL4
NM_004260.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 5.21

Publications

2 publications found

Variant links:

COSMIC-nc: COSV105873990

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]

RECQL4 Gene-Disease associations (from GenCC):

Baller-Gerold syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
Rothmund-Thomson syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Rothmund-Thomson syndrome type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, G2P
osteosarcoma
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
rapadilino syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
congenital heart disease
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

RECQL4 links:

ENSG00000265393 (HGNC:):

ENSG00000265393 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.84

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RECQL4	NM_004260.4	MANE Select	c.2434G>A	p.Ala812Thr	missense	Exon 14 of 21	NP_004251.4	O94761
RECQL4	NM_001413019.1		c.2434G>A	p.Ala812Thr	missense	Exon 14 of 20	NP_001399948.1
RECQL4	NM_001413036.1		c.2434G>A	p.Ala812Thr	missense	Exon 14 of 21	NP_001399965.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.2434G>A	p.Ala812Thr	missense	Exon 14 of 21	ENSP00000482313.2	O94761
RECQL4	ENST00000621189.4	TSL:1	c.1363G>A	p.Ala455Thr	missense	Exon 13 of 20	ENSP00000483145.1	A0A087X072
RECQL4	ENST00000971710.1		c.2341G>A	p.Ala781Thr	missense	Exon 14 of 21	ENSP00000641769.1

Frequencies

GnomAD3 genomes

AF:

0.0000660

AC:

AN:

151506

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000948

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000926

AC:

AN:

216054

AF XY:

0.0000747

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000893

Gnomad NFE exome

AF:

0.000164

Gnomad OTH exome

AF:

0.000366

GnomAD4 exome

AF:

0.000154

AC:

221

AN:

1434562

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

114

AN XY:

711964

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33210

American (AMR)

AF:

0.0000227

AC:

AN:

44076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25872

East Asian (EAS)

AF:

0.00

AC:

AN:

39218

South Asian (SAS)

AF:

0.00

AC:

AN:

85480

European-Finnish (FIN)

AF:

0.000104

AC:

AN:

38294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5312

European-Non Finnish (NFE)

AF:

0.000190

AC:

210

AN:

1103584

Other (OTH)

AF:

0.0000840

AC:

AN:

59516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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

AF:

0.0000660

AC:

AN:

151506

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

73982

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40978

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000948

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

67956

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000210

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000124

AC:

ExAC

AF:

0.0000848

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Baller-Gerold syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.16

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.29

MetaRNN

Pathogenic

0.84

MutationAssessor

Uncertain

2.8

PhyloP100

5.2

PrimateAI

Uncertain

0.59

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.88

MVP

0.67

GERP RS

5.6

PromoterAI

-0.0028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.75

gMVP

0.61

Mutation Taster

=41/59

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over