Genetic Variant CELSR2:c.5464+33A>T (chr1-109264661-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001408.3(CELSR2):c.5464+33A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,600,146 control chromosomes in the GnomAD database, including 12,076 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1197 hom., cov: 33)

Exomes 𝑓: 0.12 ( 10879 hom. )

Consequence

CELSR2
NM_001408.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.711

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELSR2	NM_001408.3 link	c.5464+33A>T		intron_variant	Intron 11 of 33	ENST00000271332.4	NP_001399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELSR2	ENST00000271332.4 link	c.5464+33A>T		intron_variant	Intron 11 of 33	1	NM_001408.3	ENSP00000271332.3		Q9HCU4

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17944

AN:

152144

Hom.:

1194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.0887

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.0885

Gnomad FIN

AF:

0.0966

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.101

AC:

24986

AN:

247416

Hom.:

1462

AF XY:

0.102

AC XY:

13641

AN XY:

133724

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.0596

Gnomad ASJ exome

AF:

0.134

Gnomad EAS exome

AF:

0.00207

Gnomad SAS exome

AF:

0.0893

Gnomad FIN exome

AF:

0.0973

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.0954

GnomAD4 exome

AF:

0.119

AC:

172544

AN:

1447884

Hom.:

10879

Cov.:

AF XY:

0.118

AC XY:

84563

AN XY:

717236

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.0629

Gnomad4 ASJ exome

AF:

0.132

Gnomad4 EAS exome

AF:

0.00221

Gnomad4 SAS exome

AF:

0.0901

Gnomad4 FIN exome

AF:

0.0965

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.118

AC:

17967

AN:

152262

Hom.:

1197

Cov.:

AF XY:

0.115

AC XY:

8583

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.140

Gnomad4 AMR

AF:

0.0885

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.0884

Gnomad4 FIN

AF:

0.0966

Gnomad4 NFE

AF:

0.125

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.0787

Hom.:

110

Bravo

AF:

0.121

Asia WGS

AF:

0.0550

AC:

192

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.65

DANN

Benign

0.68

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over