rs7528419

Positions:

• chr1-109274570-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CELSR2	NM_001408.3	c.*521A>G		3_prime_UTR_variant	34/34	ENST00000271332.4	NP_001399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELSR2	ENST00000271332.4	c.*521A>G		3_prime_UTR_variant	34/34	1	NM_001408.3	ENSP00000271332	P1
CELSR2	ENST00000498157.1	n.2643A>G		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34583 AN: 152002 Hom.: 4141 Cov.: 32

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.: 0 AF XY: 0.186 AC XY: 1086 AN XY: 5846

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.0679

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.228 AC: 34626 AN: 152120 Hom.: 4150 Cov.: 32 AF XY: 0.228 AC XY: 16980 AN XY: 74370

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.0631

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.216

Alfa AF: 0.215 Hom.: 6603

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
DANN	Benign	0.45

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

Other links and lift over

dbSNP: rs7528419; hg19: chr1-109817192; COSMIC: COSV105049602; COSMIC: COSV105049602;