GeneBe

rs786201016

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2

The NM_001378328.1(CELSR1):​c.5721_5724delTGTG​(p.Cys1907TrpfsTer6) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000685 in 1,460,608 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CELSR1
NM_001378328.1 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.03

Publications

0 publications found
Variant links:
Genes affected
CELSR1 (HGNC:1850): (cadherin EGF LAG seven-pass G-type receptor 1) 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. This particular member is a developmentally regulated, neural-specific gene which plays an unspecified role in early embryogenesis. [provided by RefSeq, Jul 2008]
CELSR1 Gene-Disease associations (from GenCC):
  • lymphatic malformation 9
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • neural tube defects, susceptibility to
    Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae)
  • epilepsy
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
  • hydrops fetalis
    Inheritance: AD Classification: LIMITED Submitted by: G2P
  • genetic developmental and epileptic encephalopathy
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CELSR1NM_001378328.1 linkc.5721_5724delTGTG p.Cys1907TrpfsTer6 frameshift_variant Exon 13 of 35 ENST00000674500.2 NP_001365257.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CELSR1ENST00000674500.2 linkc.5721_5724delTGTG p.Cys1907TrpfsTer6 frameshift_variant Exon 13 of 35 NM_001378328.1 ENSP00000501367.2 A0A6I8PRU0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460608
Hom.:
0
AF XY:
0.00000138
AC XY:
1
AN XY:
726474
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33440
American (AMR)
AF:
0.00
AC:
0
AN:
44576
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26080
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39632
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85966
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53304
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1111508
Other (OTH)
AF:
0.00
AC:
0
AN:
60338
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
4.0

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

Other links and lift over

dbSNP: rs786201016; hg19: chr22-46792620; API