chr6-21065218-C-A

Position:

• chr6-21065218-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.1226C>A	p.Pro409Gln	missense_variant	12/16	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1226C>A	p.Pro409Gln	missense_variant	12/16	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.1226C>A	p.Pro409Gln	missense_variant	10/14	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.9	H;H
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-7.0	D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.016	D;D
Sift4G	Uncertain	0.021	D;D
Polyphen		0.76	P;P
Vest4		0.45
MutPred		0.37		Gain of MoRF binding (P = 0.0484);Gain of MoRF binding (P = 0.0484);
MVP		0.24
MPC		0.83
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.63
gMVP		0.83

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

Other links and lift over

dbSNP: rs77152992; hg19: chr6-21065449;