rs77152992

Variant names:

• chr6-21065218-C-A
• rs77152992
• NM_017774.3:c.1226C>A
• CDKAL1 p.Pro409Gln

Your query was ambiguous. Multiple possible variants found:

• chr6-21065218-C-A
• chr6-21065218-C-G
• chr6-21065218-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017774.3(CDKAL1):​c.1226C>A​(p.Pro409Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDKAL1 NM_017774.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.66
• Publications: 25 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1226C>A	p.Pro409Gln	missense	Exon 12 of 16	NP_060244.2	Q5VV42-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.1226C>A	p.Pro409Gln	missense	Exon 12 of 16	ENSP00000274695.4	Q5VV42-1
	CDKAL1	ENST00000946780.1		c.1334C>A	p.Pro445Gln	missense	Exon 13 of 17	ENSP00000616839.1
	CDKAL1	ENST00000378610.1	TSL:2	c.1226C>A	p.Pro409Gln	missense	Exon 10 of 14	ENSP00000367873.1	Q5VV42-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.73	D
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		5.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.021	D
Varity_R		0.63
gMVP		0.83
Mutation Taster		=52/48	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs77152992;

hg19: chr6-21065449;