Variant 1-109272630-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001408.3(CELSR2):c.8055-10A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,610,362 control chromosomes in the GnomAD database, including 76,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7667 hom., cov: 32)

Exomes 𝑓: 0.30 ( 68980 hom. )

Consequence

CELSR2
NM_001408.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001355

Clinical Significance

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

Conservation

PhyloP100: -0.677

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-109272630-A-G is Benign according to our data. Variant chr1-109272630-A-G is described in ClinVar as [Benign]. Clinvar id is 1530644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 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.8055-10A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000271332.4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
CELSR2	ENST00000271332.4 linkuse as main transcript	c.8055-10A>G	splice_polypyrimidine_tract_variant, intron_variant		1	NM_001408.3	P1
CELSR2	ENST00000489018.1 linkuse as main transcript	n.1971A>G	non_coding_transcript_exon_variant	5/9	5
CELSR2	ENST00000498157.1 linkuse as main transcript	n.851-10A>G	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47126

AN:

151878

Hom.:

7656

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.0642

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.294

GnomAD3 exomes

AF:

0.282

AC:

69921

AN:

247816

Hom.:

10573

AF XY:

0.283

AC XY:

38119

AN XY:

134532

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.239

Gnomad ASJ exome

AF:

0.299

Gnomad EAS exome

AF:

0.0648

Gnomad SAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.338

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.276

GnomAD4 exome

AF:

0.304

AC:

442987

AN:

1458364

Hom.:

68980

Cov.:

AF XY:

0.302

AC XY:

219069

AN XY:

725640

show subpopulations

Gnomad4 AFR exome

AF:

0.336

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.302

Gnomad4 EAS exome

AF:

0.0692

Gnomad4 SAS exome

AF:

0.267

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.316

Gnomad4 OTH exome

AF:

0.299

GnomAD4 genome

AF:

0.310

AC:

47164

AN:

151998

Hom.:

7667

Cov.:

AF XY:

0.310

AC XY:

23032

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.336

Gnomad4 AMR

AF:

0.274

Gnomad4 ASJ

AF:

0.296

Gnomad4 EAS

AF:

0.0639

Gnomad4 SAS

AF:

0.263

Gnomad4 FIN

AF:

0.346

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.292

Alfa

AF:

0.309

Hom.:

4498

Bravo

AF:

0.307

Asia WGS

AF:

0.175

AC:

609

AN:

3478

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 21, 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

-0.79

CADD

Benign

3.7

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.020

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