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

Variant summary

Our verdict is Likely benign. The variant received -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. 12/21 in silico tools predict 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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

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

BS2

High AC in GnomAdExome4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152342.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDYL2	NM_152342.4	MANE Select	c.1160G>A	p.Arg387His	missense	Exon 5 of 7	NP_689555.2	Q8N8U2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDYL2	ENST00000570137.7	TSL:1 MANE Select	c.1160G>A	p.Arg387His	missense	Exon 5 of 7	ENSP00000476295.1	Q8N8U2
CDYL2	ENST00000562812.5	TSL:5	c.1163G>A	p.Arg388His	missense	Exon 6 of 8	ENSP00000454546.1	A0A0B4J291
CDYL2	ENST00000563890.5	TSL:5	c.1163G>A	p.Arg388His	missense	Exon 6 of 8	ENSP00000455111.1	A0A0B4J291

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

250912

AF XY:

0.0000295

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 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

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.0000895

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5160

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1111922

Other (OTH)

AF:

0.00

AC:

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

Eigen

Benign

0.017

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.011

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.12

PhyloP100

6.1

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.43

Sift

Benign

0.085

Sift4G

Benign

0.13

Polyphen

0.034

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

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over