chr16-80604501-C-A

Variant names:

• chr16-80604501-C-A
• rs570302046
• NM_152342.4:c.1408G>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_152342.4(CDYL2):​c.1408G>T​(p.Val470Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• 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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31683886).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDYL2	NM_152342.4	c.1408G>T	p.Val470Leu	missense_variant	Exon 7 of 7	ENST00000570137.7	NP_689555.2
CDYL2	XM_011522866.2	c.1510G>T	p.Val504Leu	missense_variant	Exon 7 of 7		XP_011521168.1
CDYL2	XM_011522867.3	c.1399G>T	p.Val467Leu	missense_variant	Exon 7 of 7		XP_011521169.1
CDYL2	XM_024450151.2	c.1231G>T	p.Val411Leu	missense_variant	Exon 7 of 7		XP_024305919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDYL2	ENST00000570137.7	c.1408G>T	p.Val470Leu	missense_variant	Exon 7 of 7	1	NM_152342.4	ENSP00000476295.1
CDYL2	ENST00000562812.5	c.1411G>T	p.Val471Leu	missense_variant	Exon 8 of 8	5		ENSP00000454546.1
CDYL2	ENST00000563890.5	c.1411G>T	p.Val471Leu	missense_variant	Exon 8 of 8	5		ENSP00000455111.1
CDYL2	ENST00000566173.3	c.1411G>T	p.Val471Leu	missense_variant	Exon 8 of 8	5		ENSP00000456934.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727246

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: 0.00000719

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1408G>T (p.V470L) alteration is located in exon 7 (coding exon 7) of the CDYL2 gene. This alteration results from a G to T substitution at nucleotide position 1408, causing the valine (V) at amino acid position 470 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	Benign	0.16
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T;.;.;.
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;.;.;D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.67	.;N;N;N
Sift	Benign	0.033	.;D;D;D
Sift4G	Benign	0.26	T;T;T;T
Polyphen		0.17	B;.;.;.
Vest4		0.23
MutPred		0.46		Loss of helix (P = 0.0558);.;.;.;
MVP		0.29
MPC		0.34
ClinPred		0.78	D
GERP RS		5.2
Varity_R		0.077
gMVP		0.80

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: rs570302046; hg19: chr16-80638398;