chr16-80604501-C-A

Variant summary

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

The NM_152342.4(CDYL2):​c.1408G>T​(p.Val470Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,890 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CDYL2
NM_152342.4 missense

Scores

1
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
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]

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=0.31683886).
BS2
High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDYL2NM_152342.4 linkc.1408G>T p.Val470Leu missense_variant Exon 7 of 7 ENST00000570137.7 NP_689555.2 Q8N8U2
CDYL2XM_011522866.2 linkc.1510G>T p.Val504Leu missense_variant Exon 7 of 7 XP_011521168.1
CDYL2XM_011522867.3 linkc.1399G>T p.Val467Leu missense_variant Exon 7 of 7 XP_011521169.1
CDYL2XM_024450151.2 linkc.1231G>T p.Val411Leu missense_variant Exon 7 of 7 XP_024305919.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDYL2ENST00000570137.7 linkc.1408G>T p.Val470Leu missense_variant Exon 7 of 7 1 NM_152342.4 ENSP00000476295.1 Q8N8U2
CDYL2ENST00000562812.5 linkc.1411G>T p.Val471Leu missense_variant Exon 8 of 8 5 ENSP00000454546.1 A0A0B4J291
CDYL2ENST00000563890.5 linkc.1411G>T p.Val471Leu missense_variant Exon 8 of 8 5 ENSP00000455111.1 A0A0B4J291
CDYL2ENST00000566173.3 linkc.1411G>T p.Val471Leu missense_variant Exon 8 of 8 5 ENSP00000456934.1 A0A0B4J291

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727246
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:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000312
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 05, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1408G>T (p.V470L) alteration is located in exon 7 (coding exon 7) of the CDYL2 gene. This alteration results from a G to T substitution at nucleotide position 1408, causing the valine (V) at amino acid position 470 to be replaced by a leucine (L). 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
0.16
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.039
T;.;.;.
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.87
D;.;.;D
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.32
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N;.;.;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.67
.;N;N;N
Sift
Benign
0.033
.;D;D;D
Sift4G
Benign
0.26
T;T;T;T
Polyphen
0.17
B;.;.;.
Vest4
0.23
MutPred
0.46
Loss of helix (P = 0.0558);.;.;.;
MVP
0.29
MPC
0.34
ClinPred
0.78
D
GERP RS
5.2
Varity_R
0.077
gMVP
0.80

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.

Other links and lift over

dbSNP: rs570302046; hg19: chr16-80638398; API