Variant 6-21198076-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017774.3(CDKAL1):c.1355A>T(p.Tyr452Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000941 in 1,604,390 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000095 ( 1 hom. )

Consequence

CDKAL1
NM_017774.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.45

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009580076).

BP6

Variant 6-21198076-A-T is Benign according to our data. Variant chr6-21198076-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 715336.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKAL1	NM_017774.3 linkuse as main transcript	c.1355A>T	p.Tyr452Phe	missense_variant	14/16	ENST00000274695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8 linkuse as main transcript	c.1355A>T	p.Tyr452Phe	missense_variant	14/16	1	NM_017774.3	P1	Q5VV42-1
CDKAL1	ENST00000378610.1 linkuse as main transcript	c.1355A>T	p.Tyr452Phe	missense_variant	12/14	2		P1	Q5VV42-1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000176

AC:

AN:

244846

Hom.:

AF XY:

0.000181

AC XY:

AN XY:

132416

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00227

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000342

GnomAD4 exome

AF:

0.0000950

AC:

138

AN:

1452082

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

722016

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00287

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000399

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00231

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000106

ExAC

AF:

0.000214

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

0.061

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

T;.

M_CAP

Benign

0.0059

MetaRNN

Benign

0.0096

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.079

Sift

Benign

0.23

T;T

Sift4G

Benign

0.45

T;T

Polyphen

0.049

B;B

Vest4

0.36

MVP

0.23

MPC

0.31

ClinPred

0.072

GERP RS

5.7

Varity_R

0.40

gMVP

0.45

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