chr16-80633049-C-A

Position:

• chr16-80633049-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152342.4(CDYL2):​c.804G>T​(p.Gln268His) variant causes a missense change involving the alteration of a non-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: 2.77

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.77

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDYL2	NM_152342.4	c.804G>T	p.Gln268His	missense_variant	3/7	ENST00000570137.7
CDYL2	XM_011522866.2	c.906G>T	p.Gln302His	missense_variant	3/7
CDYL2	XM_011522867.3	c.795G>T	p.Gln265His	missense_variant	3/7
CDYL2	XM_024450151.2	c.627G>T	p.Gln209His	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDYL2	ENST00000570137.7	c.804G>T	p.Gln268His	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

Feb 12, 2024

The c.804G>T (p.Q268H) alteration is located in exon 3 (coding exon 3) of the CDYL2 gene. This alteration results from a G to T substitution at nucleotide position 804, causing the glutamine (Q) at amino acid position 268 to be replaced by a histidine (H). 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	0.73
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T;.;.;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D;.;.;D
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.77	D;D;D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.83	L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.86	D
Sift4G	Uncertain	0.033	D;D;D;D
Polyphen		0.99	D;.;.;.
Vest4		0.77
MutPred		0.66		Loss of stability (P = 0.0439);.;.;.;
MVP		0.54
MPC		0.65
ClinPred		0.87	D
GERP RS		4.5
Varity_R		0.13
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-80666946;