rs649281

chr1-109256622-T-C

Variant summary

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

The NM_001408.3(CELSR2):c.3311-1810T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,052 control chromosomes in the GnomAD database, including 2,327 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 0.15 (2327 hom., cov: 32)
• Consequence: CELSR2 NM_001408.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELSR2	NM_001408.3	c.3311-1810T>C		intron_variant		ENST00000271332.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELSR2	ENST00000271332.4	c.3311-1810T>C		intron_variant		1	NM_001408.3	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22377 AN: 151934 Hom.: 2323 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.0946

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0214

Gnomad FIN AF: 0.0966

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.147 AC: 22408 AN: 152052 Hom.: 2327 Cov.: 32 AF XY: 0.143 AC XY: 10594 AN XY: 74318

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.0945

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0210

Gnomad4 FIN AF: 0.0966

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.131

Alfa AF: 0.133 Hom.: 229

Bravo AF: 0.154

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.2
Dann	Benign	0.37

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: rs649281; hg19: chr1-109799244;