16-80633049-C-G

Variant names:

• chr16-80633049-C-G
• NM_152342.4:c.804G>C
• CDYL2 p.Gln268His

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152342.4(CDYL2):​c.804G>C​(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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDYL2 NM_152342.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152342.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDYL2	NM_152342.4	MANE Select	c.804G>C	p.Gln268His	missense	Exon 3 of 7	NP_689555.2	Q8N8U2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDYL2	ENST00000570137.7	TSL:1 MANE Select	c.804G>C	p.Gln268His	missense	Exon 3 of 7	ENSP00000476295.1	Q8N8U2
	CDYL2	ENST00000562812.5	TSL:5	c.807G>C	p.Gln269His	missense	Exon 4 of 8	ENSP00000454546.1	A0A0B4J291
	CDYL2	ENST00000563890.5	TSL:5	c.807G>C	p.Gln269His	missense	Exon 4 of 8	ENSP00000455111.1	A0A0B4J291

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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	0.94	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.83	L
PhyloP100		2.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.3	N
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.033	D
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-80666946;