16-80612684-C-A

Variant names:

• chr16-80612684-C-A
• rs747855913
• NM_152342.4:c.1160G>T

Variant summary

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

The NM_152342.4(CDYL2):​c.1160G>T​(p.Arg387Leu) variant causes a missense change. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R387C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDYL2 NM_152342.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.08
• 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, 0.794

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.1160G>T	p.Arg387Leu	missense	Exon 5 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.1160G>T	p.Arg387Leu	missense	Exon 5 of 7	ENSP00000476295.1	Q8N8U2
	CDYL2	ENST00000562812.5	TSL:5	c.1163G>T	p.Arg388Leu	missense	Exon 6 of 8	ENSP00000454546.1	A0A0B4J291
	CDYL2	ENST00000563890.5	TSL:5	c.1163G>T	p.Arg388Leu	missense	Exon 6 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	0.81
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.26	N
PhyloP100		6.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.4	N
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.035	D
Polyphen		0.17	B
Vest4		0.69
MutPred		0.81		Loss of methylation at R387 (P = 0.0497)
MVP		0.42
MPC		0.57
ClinPred		0.91	D
GERP RS		5.0
Varity_R		0.32
gMVP		0.93

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

Other links and lift over

dbSNP: rs747855913; hg19: chr16-80646581;