20-35462425-C-T

Variant names:

• chr20-35462425-C-T
• rs1391330529
• NM_007186.6:c.58C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001318219.1(CEP250):​c.-1842C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,200 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CEP250 NM_001318219.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.22
• Publications: 0 publications found

Genes affected

CEP250 (HGNC:1859): (centrosomal protein 250) This gene encodes a core centrosomal protein required for centriole-centriole cohesion during interphase of the cell cycle. The encoded protein dissociates from the centrosomes when parental centrioles separate at the beginning of mitosis. The protein associates with and is phosphorylated by NIMA-related kinase 2, which is also associated with the centrosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

CEP250 Gene-Disease associations (from GenCC):

• cone-rod dystrophy and hearing loss 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: NO_KNOWN Submitted by: King Faisal Specialist Hospital and Research Center

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=-0.37).
• BP6: Variant 20-35462425-C-T is Benign according to our data. Variant chr20-35462425-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1126175.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318219.1. 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
	CEP250	NM_007186.6	MANE Select	c.58C>T	p.Leu20Leu	synonymous	Exon 4 of 35	NP_009117.2
	CEP250	NM_001318219.1		c.-1842C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 33	NP_001305148.1	Q9BV73
	CEP250	NM_001318219.1		c.-1842C>T		5_prime_UTR	Exon 2 of 33	NP_001305148.1	Q9BV73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP250	ENST00000397527.6	TSL:5 MANE Select	c.58C>T	p.Leu20Leu	synonymous	Exon 4 of 35	ENSP00000380661.1	Q9BV73-1
	CEP250	ENST00000446710.5	TSL:1	c.58C>T	p.Leu20Leu	synonymous	Exon 4 of 7	ENSP00000398747.1	Q5JWS5
	CEP250	ENST00000706828.1		c.58C>T	p.Leu20Leu	synonymous	Exon 4 of 36	ENSP00000516576.1	A0A9L9PXX3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 228892 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450200 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 720256

African (AFR) AF: 0.00 AC: 0 AN: 33254

American (AMR) AF: 0.00 AC: 0 AN: 42972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25852

East Asian (EAS) AF: 0.00 AC: 0 AN: 39180

South Asian (SAS) AF: 0.00 AC: 0 AN: 84250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1106316

Other (OTH) AF: 0.00 AC: 0 AN: 59928

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Benign	0.67
PhyloP100		2.2
PromoterAI		-0.017	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1391330529; hg19: chr20-34050250;