Variant 6-20546472-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017774.3(CDKAL1):c.122G>A(p.Arg41Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000768 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

CDKAL1
NM_017774.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.91

Variant links:

Genes affected

CDKAL1 (HGNC:21050): (CDK5 regulatory subunit associated protein 1 like 1) The protein encoded by this gene is a member of the methylthiotransferase family. The function of this gene is not known. Genome-wide association studies have linked single nucleotide polymorphisms in an intron of this gene with susceptibilty to type 2 diabetes. [provided by RefSeq, May 2010]

CDKAL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029218584).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKAL1	NM_017774.3 linkuse as main transcript	c.122G>A	p.Arg41Gln	missense_variant	3/16	ENST00000274695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8 linkuse as main transcript	c.122G>A	p.Arg41Gln	missense_variant	3/16	1	NM_017774.3	P1	Q5VV42-1
CDKAL1	ENST00000613575.4 linkuse as main transcript	c.122G>A	p.Arg41Gln	missense_variant	4/6	1			Q5VV42-3
CDKAL1	ENST00000378610.1 linkuse as main transcript	c.122G>A	p.Arg41Gln	missense_variant	1/14	2		P1	Q5VV42-1

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000119

AC:

AN:

251364

Hom.:

AF XY:

0.0000957

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000561

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000276

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000669

Hom.:

Bravo

AF:

0.000295

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.122G>A (p.R41Q) alteration is located in exon 3 (coding exon 1) of the CDKAL1 gene. This alteration results from a G to A substitution at nucleotide position 122, causing the arginine (R) at amino acid position 41 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.34

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.91

D;D;.

M_CAP

Benign

0.0081

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.79

D;D;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.88

N;.;N

REVEL

Benign

0.098

Sift

Benign

0.047

D;.;D

Sift4G

Benign

0.098

T;T;T

Polyphen

0.041

B;P;B

Vest4

0.40

MVP

0.45

MPC

0.37

ClinPred

0.037

GERP RS

5.5

Varity_R

0.12

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over