16-80612646-G-T

Position:

• chr16-80612646-G-T

Variant summary

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

The NM_152342.4(CDYL2):​c.1198C>A​(p.Gln400Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,156 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CDYL2 NM_152342.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.05

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.1198C>A	p.Gln400Lys	missense_variant	5/7	ENST00000570137.7	NP_689555.2
CDYL2	XM_011522866.2	c.1300C>A	p.Gln434Lys	missense_variant	5/7		XP_011521168.1
CDYL2	XM_011522867.3	c.1189C>A	p.Gln397Lys	missense_variant	5/7		XP_011521169.1
CDYL2	XM_024450151.2	c.1021C>A	p.Gln341Lys	missense_variant	5/7		XP_024305919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDYL2	ENST00000570137.7	c.1198C>A	p.Gln400Lys	missense_variant	5/7	1	NM_152342.4	ENSP00000476295.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458156 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725280

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: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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 08, 2024

The c.1198C>A (p.Q400K) alteration is located in exon 5 (coding exon 5) of the CDYL2 gene. This alteration results from a C to A substitution at nucleotide position 1198, causing the glutamine (Q) at amino acid position 400 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	Uncertain	0.48
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	23
DANN	Benign	0.73
DEOGEN2	Benign	0.029	T;.;.;.
Eigen	Benign	-0.22
Eigen_PC	Benign	0.044
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	D;.;.;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.33	N;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	1.1	.;N;N;N
Sift	Benign	1.0	.;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.018	B;.;.;.
Vest4		0.73
MutPred		0.51		Gain of methylation at Q400 (P = 0.0067);.;.;.;
MVP		0.81
MPC		0.69
ClinPred		0.87	D
GERP RS		4.7
Varity_R		0.26
gMVP		0.83

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: rs1906650478; hg19: chr16-80646543;