chr16-80633194-A-G

Position:

• chr16-80633194-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152342.4(CDYL2):​c.659T>C​(p.Val220Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: CDYL2 NM_152342.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26213717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDYL2	NM_152342.4	c.659T>C	p.Val220Ala	missense_variant	3/7	ENST00000570137.7
CDYL2	XM_011522866.2	c.761T>C	p.Val254Ala	missense_variant	3/7
CDYL2	XM_011522867.3	c.650T>C	p.Val217Ala	missense_variant	3/7
CDYL2	XM_024450151.2	c.482T>C	p.Val161Ala	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDYL2	ENST00000570137.7	c.659T>C	p.Val220Ala	missense_variant	3/7	1	NM_152342.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.659T>C (p.V220A) alteration is located in exon 3 (coding exon 3) of the CDYL2 gene. This alteration results from a T to C substitution at nucleotide position 659, causing the valine (V) at amino acid position 220 to be replaced by an alanine (A). 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	0.076
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T;.;.;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.71	T;.;.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.97	L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.5	.;N;N;N
Sift	Benign	0.039	.;D;D;D
Sift4G	Benign	0.093	T;T;T;T
Polyphen		0.89	P;.;.;.
Vest4		0.25
MutPred		0.32		Loss of methylation at K221 (P = 0.0454);.;.;.;
MVP		0.33
MPC		0.19
ClinPred		0.85	D
GERP RS		5.0
Varity_R		0.083
gMVP		0.52

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.

Other links and lift over

hg19: chr16-80667091; COSMIC: COSV73655120; COSMIC: COSV73655120;