Variant 16-80604457-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_152342.4(CDYL2):c.1452G>C(p.Gln484His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

CDYL2
NM_152342.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.484

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36189005).

BS2

High AC in GnomAdExome4 at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDYL2	NM_152342.4 link	c.1452G>C	p.Gln484His	missense_variant	7/7	ENST00000570137.7	NP_689555.2	Q8N8U2
CDYL2	XM_011522866.2 link	c.1554G>C	p.Gln518His	missense_variant	7/7		XP_011521168.1
CDYL2	XM_011522867.3 link	c.1443G>C	p.Gln481His	missense_variant	7/7		XP_011521169.1
CDYL2	XM_024450151.2 link	c.1275G>C	p.Gln425His	missense_variant	7/7		XP_024305919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDYL2	ENST00000570137.7 link	c.1452G>C	p.Gln484His	missense_variant	7/7	1	NM_152342.4	ENSP00000476295.1	Q8N8U2
CDYL2	ENST00000562812.5 link	c.1455G>C	p.Gln485His	missense_variant	8/8	5		ENSP00000454546.1	A0A0B4J291
CDYL2	ENST00000563890.5 link	c.1455G>C	p.Gln485His	missense_variant	8/8	5		ENSP00000455111.1	A0A0B4J291
CDYL2	ENST00000566173.3 link	c.1455G>C	p.Gln485His	missense_variant	8/8	5		ENSP00000456934.1	A0A0B4J291

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251488

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.1452G>C (p.Q484H) alteration is located in exon 7 (coding exon 7) of the CDYL2 gene. This alteration results from a G to C substitution at nucleotide position 1452, causing the glutamine (Q) at amino acid position 484 to be replaced by a histidine (H). 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

Benign

0.28

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.078

T;.;.;.

Eigen

Benign

0.023

Eigen_PC

Benign

-0.050

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;.;.;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.36

T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.6

L;.;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-2.1

.;N;N;N

Sift

Uncertain

0.0060

.;D;D;D

Sift4G

Uncertain

0.018

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.51

MutPred

0.38

Gain of ubiquitination at K483 (P = 0.1079);.;.;.;

MVP

0.44

MPC

0.65

ClinPred

0.84

GERP RS

-1.0

Varity_R

0.26

gMVP

0.62

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