16-80612793-C-G

Position:

• chr16-80612793-C-G

Variant summary

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

The NM_152342.4(CDYL2):​c.1051G>C​(p.Val351Leu) variant causes a missense change. 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: 6.17

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]

CDYL2 (HGNC:):

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.1051G>C	p.Val351Leu	missense_variant	5/7	ENST00000570137.7	NP_689555.2
CDYL2	XM_011522866.2	c.1153G>C	p.Val385Leu	missense_variant	5/7		XP_011521168.1
CDYL2	XM_011522867.3	c.1042G>C	p.Val348Leu	missense_variant	5/7		XP_011521169.1
CDYL2	XM_024450151.2	c.874G>C	p.Val292Leu	missense_variant	5/7		XP_024305919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDYL2	ENST00000570137.7	c.1051G>C	p.Val351Leu	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

Dec 17, 2023

The c.1051G>C (p.V351L) alteration is located in exon 5 (coding exon 5) of the CDYL2 gene. This alteration results from a G to C substitution at nucleotide position 1051, causing the valine (V) at amino acid position 351 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	0.93
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T;.;.;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;.;.;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.46	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.7	.;N;N;N
Sift	Uncertain	0.019	.;D;D;D
Sift4G	Uncertain	0.039	D;D;D;D
Polyphen		0.87	P;.;.;.
Vest4		0.57
MutPred		0.69		Loss of methylation at K347 (P = 0.0718);.;.;.;
MVP		0.44
MPC		0.17
ClinPred		0.83	D
GERP RS		4.1
Varity_R		0.25
gMVP		0.92

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: chr16-80646690;