16-80633069-G-A

Position:

• chr16-80633069-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152342.4(CDYL2):​c.784C>T​(p.His262Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 9.32

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDYL2	NM_152342.4	c.784C>T	p.His262Tyr	missense_variant	3/7	ENST00000570137.7	NP_689555.2
CDYL2	XM_011522866.2	c.886C>T	p.His296Tyr	missense_variant	3/7		XP_011521168.1
CDYL2	XM_011522867.3	c.775C>T	p.His259Tyr	missense_variant	3/7		XP_011521169.1
CDYL2	XM_024450151.2	c.607C>T	p.His203Tyr	missense_variant	3/7		XP_024305919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDYL2	ENST00000570137.7	c.784C>T	p.His262Tyr	missense_variant	3/7	1	NM_152342.4	ENSP00000476295.1

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

Jul 30, 2024

The c.784C>T (p.H262Y) alteration is located in exon 3 (coding exon 3) of the CDYL2 gene. This alteration results from a C to T substitution at nucleotide position 784, causing the histidine (H) at amino acid position 262 to be replaced by a tyrosine (Y). 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	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;.;.;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;.;.;D
M_CAP	Benign	0.025	D
MetaRNN	Pathogenic	0.87	D;D;D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.3	L;.;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.1	.;D;D;D
Sift	Uncertain	0.0030	.;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.96
MutPred		0.54		Loss of disorder (P = 0.0751);.;.;.;
MVP		0.64
MPC		0.72
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.47
gMVP		0.73

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: chr16-80666966;