rs2302759

Variant names:

• chr16-50793690-A-C
• rs2302759
• NM_001378743.1:c.2469+26A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-50793690-A-C
• chr16-50793690-A-G
• chr16-50793690-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001378743.1(CYLD):​c.2469+26A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYLD NM_001378743.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 24 publications found

Genes affected

CYLD (HGNC:2584): (CYLD lysine 63 deubiquitinase) This gene is encodes a cytoplasmic protein with three cytoskeletal-associated protein-glycine-conserved (CAP-GLY) domains that functions as a deubiquitinating enzyme. Mutations in this gene have been associated with cylindromatosis, multiple familial trichoepithelioma, and Brooke-Spiegler syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

CYLD-AS2 (HGNC:56848): (CYLD antisense RNA 2)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYLD	NM_001378743.1	c.2469+26A>C		intron_variant	Intron 17 of 18	ENST00000427738.8	NP_001365672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYLD	ENST00000427738.8	c.2469+26A>C		intron_variant	Intron 17 of 18	5	NM_001378743.1	ENSP00000392025.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249294 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.94e-7 AC: 1 AN: 1258822 Hom.: 0 Cov.: 18 AF XY: 0.00000157 AC XY: 1 AN XY: 637146

African (AFR) AF: 0.00 AC: 0 AN: 29518

American (AMR) AF: 0.00 AC: 0 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24830

East Asian (EAS) AF: 0.00 AC: 0 AN: 38774

South Asian (SAS) AF: 0.00 AC: 0 AN: 82154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5400

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 926810

Other (OTH) AF: 0.0000187 AC: 1 AN: 53548

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.54
PhyloP100		-0.45
PromoterAI		-0.0076	Neutral

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: rs2302759; hg19: chr16-50827601;