17-78892237-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001243540.2(CEP295NL):c.267C>T(p.Gly89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00764 in 1,550,974 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (9 hom., cov: 33)
  • Exomes 𝑓: 0.0078 (55 hom.)
• Consequence: CEP295NL NM_001243540.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.34

Genes affected

CEP295NL (HGNC:44659): (CEP295 N-terminal like) Predicted to enable microtubule binding activity. Predicted to be involved in regulation of centriole replication. Predicted to be located in motile cilium. Predicted to be active in centriole; centrosome; and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TIMP2 (HGNC:11821): (TIMP metallopeptidase inhibitor 2) This gene is a member of the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. In addition to an inhibitory role against metalloproteinases, the encoded protein has a unique role among TIMP family members in its ability to directly suppress the proliferation of endothelial cells. As a result, the encoded protein may be critical to the maintenance of tissue homeostasis by suppressing the proliferation of quiescent tissues in response to angiogenic factors, and by inhibiting protease activity in tissues undergoing remodelling of the extracellular matrix. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-78892237-G-A is Benign according to our data. Variant chr17-78892237-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648382.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.34 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP295NL	NM_001243540.2	c.267C>T	p.Gly89=	synonymous_variant	3/3	ENST00000322630.3
TIMP2	NM_003255.5	c.131-18318C>T		intron_variant		ENST00000262768.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP295NL	ENST00000322630.3	c.267C>T	p.Gly89=	synonymous_variant	3/3	2	NM_001243540.2	P1
TIMP2	ENST00000262768.11	c.131-18318C>T		intron_variant		1	NM_003255.5	P1

Frequencies

GnomAD3 genomes AF: 0.00572 AC: 870 AN: 152216 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0206

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00804

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00572 AC: 859 AN: 150226 Hom.: 9 AF XY: 0.00549 AC XY: 443 AN XY: 80702

Gnomad AFR exome AF: 0.00130

Gnomad AMR exome AF: 0.000854

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00257

Gnomad FIN exome AF: 0.0185

Gnomad NFE exome AF: 0.00790

Gnomad OTH exome AF: 0.00412

GnomAD4 exome AF: 0.00785 AC: 10979 AN: 1398640 Hom.: 55 Cov.: 31 AF XY: 0.00760 AC XY: 5240 AN XY: 689830

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.000896

Gnomad4 ASJ exome AF: 0.0000794

Gnomad4 EAS exome AF: 0.0000560

Gnomad4 SAS exome AF: 0.00245

Gnomad4 FIN exome AF: 0.0190

Gnomad4 NFE exome AF: 0.00875

Gnomad4 OTH exome AF: 0.00597

GnomAD4 genome AF: 0.00571 AC: 870 AN: 152334 Hom.: 9 Cov.: 33 AF XY: 0.00626 AC XY: 466 AN XY: 74490

Gnomad4 AFR AF: 0.00154

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.0206

Gnomad4 NFE AF: 0.00804

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00594 Hom.: 2

Bravo AF: 0.00388

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

CEP295NL: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.14
Dann	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs72851220; hg19: chr17-76888319;