Variant 1-109250129-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001408.3(CELSR2):c.50T>C(p.Leu17Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000471 in 857,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00047 ( 0 hom. )

Consequence

CELSR2
NM_001408.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.65

Variant links:

Genes affected

CELSR2 (HGNC:3231): (cadherin EGF LAG seven-pass G-type receptor 2) The protein encoded by this gene is a member of the flamingo subfamily, part of the cadherin superfamily. The flamingo subfamily consists of nonclassic-type cadherins; a subpopulation that does not interact with catenins. The flamingo cadherins are located at the plasma membrane and have nine cadherin domains, seven epidermal growth factor-like repeats and two laminin A G-type repeats in their ectodomain. They also have seven transmembrane domains, a characteristic unique to this subfamily. It is postulated that these proteins are receptors involved in contact-mediated communication, with cadherin domains acting as homophilic binding regions and the EGF-like domains involved in cell adhesion and receptor-ligand interactions. The specific function of this particular member has not been determined. [provided by RefSeq, Jul 2008]

CELSR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052482486).

BP6

Variant 1-109250129-T-C is Benign according to our data. Variant chr1-109250129-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1662312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 49 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELSR2	NM_001408.3 linkuse as main transcript	c.50T>C	p.Leu17Pro	missense_variant	1/34	ENST00000271332.4	NP_001399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELSR2	ENST00000271332.4 linkuse as main transcript	c.50T>C	p.Leu17Pro	missense_variant	1/34	1	NM_001408.3	ENSP00000271332.3		Q9HCU4

Frequencies

GnomAD3 genomes

AF:

0.000458

AC:

AN:

104862

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000350

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00541

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000290

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000594

AC:

117

AN:

197102

Hom.:

AF XY:

0.000594

AC XY:

AN XY:

111026

show subpopulations

Gnomad AFR exome

AF:

0.000740

Gnomad AMR exome

AF:

0.000386

Gnomad ASJ exome

AF:

0.000121

Gnomad EAS exome

AF:

0.00334

Gnomad SAS exome

AF:

0.000331

Gnomad FIN exome

AF:

0.000288

Gnomad NFE exome

AF:

0.000414

Gnomad OTH exome

AF:

0.000428

GnomAD4 exome

AF:

0.000472

AC:

355

AN:

752572

Hom.:

Cov.:

AF XY:

0.000478

AC XY:

185

AN XY:

386626

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.000572

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00186

Gnomad4 SAS exome

AF:

0.000317

Gnomad4 FIN exome

AF:

0.000193

Gnomad4 NFE exome

AF:

0.000434

Gnomad4 OTH exome

AF:

0.000435

GnomAD4 genome

AF:

0.000467

AC:

AN:

104966

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

AN XY:

51320

show subpopulations

Gnomad4 AFR

AF:

0.000349

Gnomad4 AMR

AF:

0.000288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00542

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000290

Gnomad4 OTH

AF:

0.000715

Alfa

AF:

0.00294

Hom.:

ExAC

AF:

0.000690

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

1.7

DANN

Benign

0.72

DEOGEN2

Benign

0.074

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.28

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.050

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.15

MVP

0.29

MPC

0.62

ClinPred

0.0045

GERP RS

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.12

gMVP

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over