Genetic Variant CDYL2:p.Arg387His (chr16-80612684-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

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

The NM_152342.4(CDYL2):c.1160G>A(p.Arg387His) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,460,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R387C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CDYL2
NM_152342.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34065935).

BS2

High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDYL2	NM_152342.4 link	c.1160G>A	p.Arg387His	missense_variant	Exon 5 of 7	ENST00000570137.7	NP_689555.2	Q8N8U2
CDYL2	XM_011522866.2 link	c.1262G>A	p.Arg421His	missense_variant	Exon 5 of 7		XP_011521168.1
CDYL2	XM_011522867.3 link	c.1151G>A	p.Arg384His	missense_variant	Exon 5 of 7		XP_011521169.1
CDYL2	XM_024450151.2 link	c.983G>A	p.Arg328His	missense_variant	Exon 5 of 7		XP_024305919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDYL2	ENST00000570137.7 link	c.1160G>A	p.Arg387His	missense_variant	Exon 5 of 7	1	NM_152342.4	ENSP00000476295.1		Q8N8U2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

250912

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1460930

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726778

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

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

Jun 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1160G>A (p.R387H) alteration is located in exon 5 (coding exon 5) of the CDYL2 gene. This alteration results from a G to A substitution at nucleotide position 1160, causing the arginine (R) at amino acid position 387 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

0.20

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

T;.;.;.

Eigen

Benign

0.017

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.87

D;.;.;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.12

N;.;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.43

.;N;N;N

Sift

Benign

0.085

.;T;T;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.034

B;.;.;.

Vest4

0.29

MutPred

0.80

Loss of methylation at R387 (P = 0.0497);.;.;.;

MVP

0.33

MPC

0.20

ClinPred

0.20

GERP RS

5.0

Varity_R

0.11

gMVP

0.85

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