Variant 16-80620839-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152342.4(CDYL2):c.931C>G(p.Leu311Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,298 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: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CDYL2
NM_152342.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDYL2	NM_152342.4 link	c.931C>G	p.Leu311Val	missense_variant	4/7	ENST00000570137.7	NP_689555.2	Q8N8U2
CDYL2	XM_011522866.2 link	c.1033C>G	p.Leu345Val	missense_variant	4/7		XP_011521168.1
CDYL2	XM_011522867.3 link	c.922C>G	p.Leu308Val	missense_variant	4/7		XP_011521169.1
CDYL2	XM_024450151.2 link	c.754C>G	p.Leu252Val	missense_variant	4/7		XP_024305919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDYL2	ENST00000570137.7 link	c.931C>G	p.Leu311Val	missense_variant	4/7	1	NM_152342.4	ENSP00000476295.1		Q8N8U2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461298

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726856

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 01, 2021

The c.931C>G (p.L311V) alteration is located in exon 4 (coding exon 4) of the CDYL2 gene. This alteration results from a C to G substitution at nucleotide position 931, causing the leucine (L) at amino acid position 311 to be replaced by a valine (V). 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

0.26

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

T;.;.;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

D;.;.;D

M_CAP

Benign

0.031

MetaRNN

Pathogenic

0.87

D;D;D;D

MetaSVM

Benign

-0.38

MutationAssessor

Benign

1.5

L;.;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.9

.;N;N;N

Sift

Uncertain

0.014

.;D;D;D

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.97

D;.;.;.

Vest4

0.84

MutPred

0.59

Gain of catalytic residue at L311 (P = 0.0536);.;.;.;

MVP

0.95

MPC

0.67

ClinPred

0.86

GERP RS

3.2

Varity_R

0.14

gMVP

0.55

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over