Genetic Variant CDKAL1:c.*204C>A (chr6-21231243-C-A) – 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_017774.3(CDKAL1):c.*204C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,854 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: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CDKAL1
NM_017774.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0100

Publications

4 publications found

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:

ENSG00000287404 (HGNC:):

ENSG00000287404 links:

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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=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017774.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.*204C>A		3_prime_UTR	Exon 16 of 16	NP_060244.2	Q5VV42-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.*204C>A	3_prime_UTR	Exon 16 of 16	ENSP00000274695.4	Q5VV42-1
CDKAL1	ENST00000946780.1		c.*204C>A	3_prime_UTR	Exon 17 of 17	ENSP00000616839.1
CDKAL1	ENST00000378610.1	TSL:2	c.*204C>A	3_prime_UTR	Exon 14 of 14	ENSP00000367873.1	Q5VV42-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151854

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:

0.000190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000150

AC:

AN:

267092

Hom.:

Cov.:

AF XY:

0.0000147

AC XY:

AN XY:

136110

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8552

American (AMR)

AF:

0.00

AC:

AN:

9720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9706

East Asian (EAS)

AF:

0.00

AC:

AN:

24504

South Asian (SAS)

AF:

0.00

AC:

AN:

6934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1316

European-Non Finnish (NFE)

AF:

0.0000237

AC:

AN:

168566

Other (OTH)

AF:

0.00

AC:

AN:

17104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.613

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151854

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41304

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.000190

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67978

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00

Hom.:

1452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.1

(source)

DANN

Benign

0.77

PhyloP100

0.010

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