16-80620818-C-T

Position:

• chr16-80620818-C-T

Variant summary

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

The NM_152342.4(CDYL2):​c.952G>A​(p.Gly318Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,684 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CDYL2 NM_152342.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.09

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	UniProt
CDYL2	NM_152342.4	c.952G>A	p.Gly318Ser	missense_variant	4/7	ENST00000570137.7
CDYL2	XM_011522866.2	c.1054G>A	p.Gly352Ser	missense_variant	4/7
CDYL2	XM_011522867.3	c.943G>A	p.Gly315Ser	missense_variant	4/7
CDYL2	XM_024450151.2	c.775G>A	p.Gly259Ser	missense_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDYL2	ENST00000570137.7	c.952G>A	p.Gly318Ser	missense_variant	4/7	1	NM_152342.4	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459684 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725940

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

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

Oct 30, 2023

The c.952G>A (p.G318S) alteration is located in exon 4 (coding exon 4) of the CDYL2 gene. This alteration results from a G to A substitution at nucleotide position 952, causing the glycine (G) at amino acid position 318 to be replaced by a serine (S). 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	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T;.;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	0.061
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D;.;.;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.2	L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.44	.;N;N;N
Sift	Benign	0.62	.;T;T;T
Sift4G	Benign	0.72	T;T;T;T
Polyphen		0.14	B;.;.;.
Vest4		0.71
MutPred		0.30		Gain of phosphorylation at G318 (P = 0.022);.;.;.;
MVP		0.80
MPC		0.67
ClinPred		0.68	D
GERP RS		5.3
Varity_R		0.15
gMVP		0.68

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

LitVar

Other links and lift over

dbSNP: rs1907047240; hg19: chr16-80654715; COSMIC: COSV105379032;