Variant 6-20546466-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_017774.3(CDKAL1):c.116G>A(p.Arg39Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00769 in 1,614,084 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0079 ( 51 hom. )

Consequence

CDKAL1
NM_017774.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.95

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006807238).

BP6

Variant 6-20546466-G-A is Benign according to our data. Variant chr6-20546466-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 773467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-20546466-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKAL1	NM_017774.3 linkuse as main transcript	c.116G>A	p.Arg39Gln	missense_variant	3/16	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8 linkuse as main transcript	c.116G>A	p.Arg39Gln	missense_variant	3/16	1	NM_017774.3	ENSP00000274695	P1	Q5VV42-1
CDKAL1	ENST00000613575.4 linkuse as main transcript	c.116G>A	p.Arg39Gln	missense_variant	4/6	1		ENSP00000481755		Q5VV42-3
CDKAL1	ENST00000378610.1 linkuse as main transcript	c.116G>A	p.Arg39Gln	missense_variant	1/14	2		ENSP00000367873	P1	Q5VV42-1

Frequencies

GnomAD3 genomes

AF:

0.00570

AC:

868

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00509

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00920

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00539

AC:

1354

AN:

251394

Hom.:

AF XY:

0.00535

AC XY:

727

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.00625

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00369

Gnomad FIN exome

AF:

0.00712

Gnomad NFE exome

AF:

0.00761

Gnomad OTH exome

AF:

0.00783

GnomAD4 exome

AF:

0.00789

AC:

11536

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00778

AC XY:

5659

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00313

Gnomad4 ASJ exome

AF:

0.00597

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00377

Gnomad4 FIN exome

AF:

0.00685

Gnomad4 NFE exome

AF:

0.00909

Gnomad4 OTH exome

AF:

0.00619

GnomAD4 genome

AF:

0.00571

AC:

869

AN:

152292

Hom.:

Cov.:

AF XY:

0.00520

AC XY:

387

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00509

Gnomad4 NFE

AF:

0.00920

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00770

Hom.:

Bravo

AF:

0.00529

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.0101

AC:

ExAC

AF:

0.00536

AC:

651

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00725

EpiControl

AF:

0.00741

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

T;.;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.92

D;D;.

MetaRNN

Benign

0.0068

T;T;T

MetaSVM

Benign

-0.83

MutationTaster

Benign

0.99

D;D;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.3

N;.;N

REVEL

Benign

0.15

Sift

Benign

0.091

T;.;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.95

P;D;P

Vest4

0.61

MVP

0.31

MPC

0.93

ClinPred

0.034

GERP RS

5.5

Varity_R

0.15

gMVP

0.57

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

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