Variant 16-80608211-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_152342.4(CDYL2):c.1243C>T(p.Arg415Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000378 in 1,586,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CDYL2
NM_152342.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.68

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 -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.858

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CDYL2	NM_152342.4 linkuse as main transcript	c.1243C>T	p.Arg415Trp	missense_variant	6/7	ENST00000570137.7
CDYL2	XM_011522866.2 linkuse as main transcript	c.1345C>T	p.Arg449Trp	missense_variant	6/7
CDYL2	XM_011522867.3 linkuse as main transcript	c.1234C>T	p.Arg412Trp	missense_variant	6/7
CDYL2	XM_024450151.2 linkuse as main transcript	c.1066C>T	p.Arg356Trp	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CDYL2	ENST00000570137.7 linkuse as main transcript	c.1243C>T	p.Arg415Trp	missense_variant	6/7	1	NM_152342.4	P4
CDYL2	ENST00000562812.5 linkuse as main transcript	c.1246C>T	p.Arg416Trp	missense_variant	7/8	5		A1
CDYL2	ENST00000563890.5 linkuse as main transcript	c.1246C>T	p.Arg416Trp	missense_variant	7/8	5		A1
CDYL2	ENST00000566173.3 linkuse as main transcript	c.1246C>T	p.Arg416Trp	missense_variant	7/8	5		A1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152144

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

GnomAD4 exome

AF:

0.00000349

AC:

AN:

1434568

Hom.:

Cov.:

AF XY:

0.00000422

AC XY:

AN XY:

710874

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000260

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000364

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74310

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

Bravo

AF:

0.00000756

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

Nov 22, 2022

The c.1243C>T (p.R415W) alteration is located in exon 6 (coding exon 6) of the CDYL2 gene. This alteration results from a C to T substitution at nucleotide position 1243, causing the arginine (R) at amino acid position 415 to be replaced by a tryptophan (W). 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

0.98

BayesDel_addAF

Uncertain

0.089

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

T;.;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.93

D;.;.;D

M_CAP

Benign

0.026

MetaRNN

Pathogenic

0.86

D;D;D;D

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.5

M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-5.7

.;D;D;D

Sift

Uncertain

0.025

.;D;D;D

Sift4G

Uncertain

0.033

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.97

MutPred

0.65

Loss of phosphorylation at T418 (P = 0.0575);.;.;.;

MVP

0.48

MPC

0.32

ClinPred

0.99

GERP RS

1.6

Varity_R

0.37

gMVP

0.82

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