16-80620818-C-T

Variant names:

• chr16-80620818-C-T
• rs1907047240
• NM_152342.4:c.952G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152342.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDYL2	NM_152342.4	MANE Select	c.952G>A	p.Gly318Ser	missense	Exon 4 of 7	NP_689555.2	Q8N8U2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDYL2	ENST00000570137.7	TSL:1 MANE Select	c.952G>A	p.Gly318Ser	missense	Exon 4 of 7	ENSP00000476295.1	Q8N8U2
	CDYL2	ENST00000562812.5	TSL:5	c.955G>A	p.Gly319Ser	missense	Exon 5 of 8	ENSP00000454546.1	A0A0B4J291
	CDYL2	ENST00000563890.5	TSL:5	c.955G>A	p.Gly319Ser	missense	Exon 5 of 8	ENSP00000455111.1	A0A0B4J291

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

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.00 AC: 0 AN: 85992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110608

Other (OTH) AF: 0.0000166 AC: 1 AN: 60290

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.1
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.44	N
Sift	Benign	0.62	T
Sift4G	Benign	0.72	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

Other links and lift over

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