16-80604537-C-T

Position:

• chr16-80604537-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152342.4(CDYL2):​c.1372G>A​(p.Glu458Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.91

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDYL2	NM_152342.4	c.1372G>A	p.Glu458Lys	missense_variant	7/7	ENST00000570137.7	NP_689555.2
CDYL2	XM_011522866.2	c.1474G>A	p.Glu492Lys	missense_variant	7/7		XP_011521168.1
CDYL2	XM_011522867.3	c.1363G>A	p.Glu455Lys	missense_variant	7/7		XP_011521169.1
CDYL2	XM_024450151.2	c.1195G>A	p.Glu399Lys	missense_variant	7/7		XP_024305919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDYL2	ENST00000570137.7	c.1372G>A	p.Glu458Lys	missense_variant	7/7	1	NM_152342.4	ENSP00000476295.1
CDYL2	ENST00000562812.5	c.1375G>A	p.Glu459Lys	missense_variant	8/8	5		ENSP00000454546.1
CDYL2	ENST00000563890.5	c.1375G>A	p.Glu459Lys	missense_variant	8/8	5		ENSP00000455111.1
CDYL2	ENST00000566173.3	c.1375G>A	p.Glu459Lys	missense_variant	8/8	5		ENSP00000456934.1

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

Nov 29, 2023

The c.1372G>A (p.E458K) alteration is located in exon 7 (coding exon 7) of the CDYL2 gene. This alteration results from a G to A substitution at nucleotide position 1372, causing the glutamic acid (E) at amino acid position 458 to be replaced by a lysine (K). 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	0.94
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T;.;.;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;.;.;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.53	D;D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.91	L;.;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.4	.;N;N;N
Sift	Benign	0.086	.;T;T;T
Sift4G	Benign	0.42	T;T;T;T
Polyphen		0.90	P;.;.;.
Vest4		0.69
MutPred		0.47		Gain of MoRF binding (P = 0.0108);.;.;.;
MVP		0.75
MPC		0.71
ClinPred		0.82	D
GERP RS		5.2
Varity_R		0.17
gMVP		0.88

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: chr16-80638434;