Genetic Variant CDYL2:p.Gln420Arg (chr16-80608195-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152342.4(CDYL2):c.1259A>G(p.Gln420Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000251 in 1,596,320 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CDYL2
NM_152342.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

Variant links:

Genes affected

CDYL2 (HGNC:23030): (chromodomain Y like 2) Predicted to enable transcription corepressor activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CDYL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
CDYL2	NM_152342.4 link	c.1259A>G	p.Gln420Arg	missense_variant	Exon 6 of 7	ENST00000570137.7	NP_689555.2	Q8N8U2
CDYL2	XM_011522866.2 link	c.1361A>G	p.Gln454Arg	missense_variant	Exon 6 of 7		XP_011521168.1
CDYL2	XM_011522867.3 link	c.1250A>G	p.Gln417Arg	missense_variant	Exon 6 of 7		XP_011521169.1
CDYL2	XM_024450151.2 link	c.1082A>G	p.Gln361Arg	missense_variant	Exon 6 of 7		XP_024305919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDYL2	ENST00000570137.7 link	c.1259A>G	p.Gln420Arg	missense_variant	Exon 6 of 7	1	NM_152342.4	ENSP00000476295.1	Q8N8U2
CDYL2	ENST00000562812.5 link	c.1262A>G	p.Gln421Arg	missense_variant	Exon 7 of 8	5		ENSP00000454546.1	A0A0B4J291
CDYL2	ENST00000563890.5 link	c.1262A>G	p.Gln421Arg	missense_variant	Exon 7 of 8	5		ENSP00000455111.1	A0A0B4J291
CDYL2	ENST00000566173.3 link	c.1262A>G	p.Gln421Arg	missense_variant	Exon 7 of 8	5		ENSP00000456934.1	A0A0B4J291

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000138

AC:

AN:

217990

Hom.:

AF XY:

0.0000171

AC XY:

AN XY:

117178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000600

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000104

Gnomad OTH exome

AF:

0.000183

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1444138

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

716388

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.06e-7

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000113

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1259A>G (p.Q420R) alteration is located in exon 6 (coding exon 6) of the CDYL2 gene. This alteration results from a A to G substitution at nucleotide position 1259, causing the glutamine (Q) at amino acid position 420 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.075

T;.;.;.

Eigen

Benign

-0.043

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.67

T;.;.;T

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.64

D;D;D;D

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.54

N;.;.;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.6

.;N;N;N

Sift

Benign

0.41

.;T;T;T

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.047

B;.;.;.

Vest4

0.88

MutPred

0.42

Gain of methylation at R425 (P = 0.05);.;.;.;

MVP

0.82

MPC

0.66

ClinPred

0.50

GERP RS

4.9

Varity_R

0.27

gMVP

0.76

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