Genetic Variant CELSR2:c.*521A>G (chr1-109274570-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001408.3(CELSR2):c.*521A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 163,362 control chromosomes in the GnomAD database, including 4,378 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 0.23 ( 4150 hom., cov: 32)

Exomes 𝑓: 0.19 ( 228 hom. )

Consequence

CELSR2
NM_001408.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.543

Publications

153 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELSR2	NM_001408.3 link	c.*521A>G		3_prime_UTR_variant	Exon 34 of 34	ENST00000271332.4	NP_001399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELSR2	ENST00000271332.4 link	c.*521A>G		3_prime_UTR_variant	Exon 34 of 34	1	NM_001408.3	ENSP00000271332.3		Q9HCU4
CELSR2	ENST00000498157.1 link	n.2643A>G		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34583

AN:

152002

Hom.:

4141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.0633

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.186

AC:

2095

AN:

11242

Hom.:

228

Cov.:

AF XY:

0.186

AC XY:

1086

AN XY:

5846

show subpopulations

African (AFR)

AF:

0.267

AC:

AN:

172

American (AMR)

AF:

0.190

AC:

265

AN:

1394

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

AN:

176

East Asian (EAS)

AF:

0.0679

AC:

AN:

604

South Asian (SAS)

AF:

0.221

AC:

172

AN:

780

European-Finnish (FIN)

AF:

0.175

AC:

111

AN:

636

Middle Eastern (MID)

AF:

0.0357

AC:

AN:

European-Non Finnish (NFE)

AF:

0.190

AC:

1310

AN:

6908

Other (OTH)

AF:

0.208

AC:

113

AN:

544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

172

258

344

430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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

AF:

0.228

AC:

34626

AN:

152120

Hom.:

4150

Cov.:

AF XY:

0.228

AC XY:

16980

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.268

AC:

11119

AN:

41492

American (AMR)

AF:

0.212

AC:

3244

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

588

AN:

3468

East Asian (EAS)

AF:

0.0631

AC:

325

AN:

5150

South Asian (SAS)

AF:

0.244

AC:

1178

AN:

4824

European-Finnish (FIN)

AF:

0.221

AC:

2347

AN:

10612

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

15041

AN:

67968

Other (OTH)

AF:

0.216

AC:

456

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1396

2791

4187

5582

6978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.219

Hom.:

15013

Bravo

AF:

0.229

Asia WGS

AF:

0.154

AC:

534

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.46

(source)

DANN

Benign

0.45

PhyloP100

-0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over