chr16-80612820-A-G

Position:

• chr16-80612820-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152342.4(CDYL2):​c.1024T>C​(p.Phe342Leu) 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 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: 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35265994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDYL2	NM_152342.4	c.1024T>C	p.Phe342Leu	missense_variant	5/7	ENST00000570137.7	NP_689555.2
CDYL2	XM_011522866.2	c.1126T>C	p.Phe376Leu	missense_variant	5/7		XP_011521168.1
CDYL2	XM_011522867.3	c.1015T>C	p.Phe339Leu	missense_variant	5/7		XP_011521169.1
CDYL2	XM_024450151.2	c.847T>C	p.Phe283Leu	missense_variant	5/7		XP_024305919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDYL2	ENST00000570137.7	c.1024T>C	p.Phe342Leu	missense_variant	5/7	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

Sep 04, 2024

The c.1024T>C (p.F342L) alteration is located in exon 5 (coding exon 5) of the CDYL2 gene. This alteration results from a T to C substitution at nucleotide position 1024, causing the phenylalanine (F) at amino acid position 342 to be replaced by a leucine (L). 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	0.99
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;.;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D;.;.;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	-0.39	N;.;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.3	.;D;D;D
Sift	Benign	0.074	.;T;T;T
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.55	P;.;.;.
Vest4		0.54
MutPred		0.63		Loss of methylation at K347 (P = 0.0932);.;.;.;
MVP		0.64
MPC		0.72
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.38
gMVP		0.78

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: chr16-80646717;