Variant 1-109264212-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001408.3(CELSR2):c.5136C>T(p.Pro1712=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 1,613,140 control chromosomes in the GnomAD database, including 162,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11706 hom., cov: 34)

Exomes 𝑓: 0.45 ( 150640 hom. )

Consequence

CELSR2
NM_001408.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -6.46

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 1-109264212-C-T is Benign according to our data. Variant chr1-109264212-C-T is described in ClinVar as [Benign]. Clinvar id is 1553618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELSR2	NM_001408.3 linkuse as main transcript	c.5136C>T	p.Pro1712=	synonymous_variant	10/34	ENST00000271332.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELSR2	ENST00000271332.4 linkuse as main transcript	c.5136C>T	p.Pro1712=	synonymous_variant	10/34	1	NM_001408.3	P1

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55120

AN:

152050

Hom.:

11704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.508

Gnomad EAS

AF:

0.469

Gnomad SAS

AF:

0.404

Gnomad FIN

AF:

0.423

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.413

GnomAD3 exomes

AF:

0.438

AC:

109231

AN:

249606

Hom.:

25022

AF XY:

0.439

AC XY:

59440

AN XY:

135288

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.498

Gnomad ASJ exome

AF:

0.498

Gnomad EAS exome

AF:

0.469

Gnomad SAS exome

AF:

0.399

Gnomad FIN exome

AF:

0.441

Gnomad NFE exome

AF:

0.461

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

AF:

0.450

AC:

657386

AN:

1460972

Hom.:

150640

Cov.:

AF XY:

0.450

AC XY:

327331

AN XY:

726796

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.487

Gnomad4 ASJ exome

AF:

0.499

Gnomad4 EAS exome

AF:

0.488

Gnomad4 SAS exome

AF:

0.401

Gnomad4 FIN exome

AF:

0.444

Gnomad4 NFE exome

AF:

0.460

Gnomad4 OTH exome

AF:

0.439

GnomAD4 genome

AF:

0.362

AC:

55135

AN:

152168

Hom.:

11706

Cov.:

AF XY:

0.362

AC XY:

26942

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.449

Gnomad4 ASJ

AF:

0.508

Gnomad4 EAS

AF:

0.469

Gnomad4 SAS

AF:

0.405

Gnomad4 FIN

AF:

0.423

Gnomad4 NFE

AF:

0.457

Gnomad4 OTH

AF:

0.415

Alfa

AF:

0.371

Hom.:

3451

Bravo

AF:

0.356

Asia WGS

AF:

0.443

AC:

1536

AN:

3478

EpiCase

AF:

0.473

EpiControl

AF:

0.483

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CELSR2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.4

DANN

Benign

0.83

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

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