Menu
GeneBe

1-109250412-C-T

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.Pro111=) 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

2

Clinical Significance

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

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.184 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1347 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CELSR2NM_001408.3 linkuse as main transcriptc.333C>T p.Pro111= synonymous_variant 1/34 ENST00000271332.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CELSR2ENST00000271332.4 linkuse as main transcriptc.333C>T p.Pro111= synonymous_variant 1/341 NM_001408.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00885
AC:
1347
AN:
152246
Hom.:
16
Cov.:
32
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.:
16
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.:
70
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00884
AC:
1347
AN:
152364
Hom.:
16
Cov.:
32
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.:
8
Bravo
AF:
0.00953
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.0146
EpiControl
AF:
0.0151

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 18, 2024- -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2023CELSR2: BP4, BP7, BS1, BS2 -

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.

Other links and lift over

dbSNP: rs142746289; hg19: chr1-109793034; COSMIC: COSV99604014; API