Variant 1-109250412-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001408.3(CELSR2):c.333C>T(p.Pro111Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,613,660 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 16 hom., cov: 32)

Exomes 𝑓: 0.012 ( 146 hom. )

Consequence

CELSR2
NM_001408.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.184

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 1-109250412-C-T is Benign according to our data. Variant chr1-109250412-C-T is described in ClinVar as [Benign]. Clinvar id is 774396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.184 with no splicing effect.

BS2

High AC in GnomAd4 at 1347 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELSR2	NM_001408.3 linkuse as main transcript	c.333C>T	p.Pro111Pro	synonymous_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.333C>T	p.Pro111Pro	synonymous_variant	1/34	1	NM_001408.3	ENSP00000271332.3		Q9HCU4

Frequencies

GnomAD3 genomes

AF:

0.00885

AC:

1347

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.00961

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0140

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00861

AC:

2160

AN:

250760

Hom.:

AF XY:

0.00843

AC XY:

1144

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.00235

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.0243

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00245

Gnomad FIN exome

AF:

0.00167

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.00979

GnomAD4 exome

AF:

0.0120

AC:

17529

AN:

1461296

Hom.:

146

Cov.:

AF XY:

0.0117

AC XY:

8471

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.00443

Gnomad4 ASJ exome

AF:

0.0254

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00259

Gnomad4 FIN exome

AF:

0.00274

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.00884

AC:

1347

AN:

152364

Hom.:

Cov.:

AF XY:

0.00825

AC XY:

615

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.00960

Gnomad4 ASJ

AF:

0.0219

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.0140

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.00953

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0146

EpiControl

AF:

0.0151

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	CELSR2: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.6

DANN

Benign

0.87

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