1-109264212-C-T

Variant names:

• chr1-109264212-C-T
• rs6698843
• NM_001408.3:c.5136C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001408.3(CELSR2):​c.5136C>T​(p.Pro1712Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 1,613,140 control chromosomes in the GnomAD database, including 162,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (11706 hom., cov: 34)
  • Exomes 𝑓: 0.45 (150640 hom.)
• Consequence: CELSR2 NM_001408.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -6.46
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 1-109264212-C-T is Benign according to our data. Variant chr1-109264212-C-T is described in ClinVar as Benign. ClinVar VariationId is 1553618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELSR2	NM_001408.3	c.5136C>T	p.Pro1712Pro	synonymous_variant	Exon 10 of 34	ENST00000271332.4	NP_001399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELSR2	ENST00000271332.4	c.5136C>T	p.Pro1712Pro	synonymous_variant	Exon 10 of 34	1	NM_001408.3	ENSP00000271332.3

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55120 AN: 152050 Hom.: 11704 Cov.: 34

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.413

GnomAD2 exomes AF: 0.438 AC: 109231 AN: 249606 AF XY: 0.439

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.498

Gnomad ASJ exome AF: 0.498

Gnomad EAS exome AF: 0.469

Gnomad FIN exome AF: 0.441

Gnomad NFE exome AF: 0.461

Gnomad OTH exome AF: 0.471

GnomAD4 exome AF: 0.450 AC: 657386 AN: 1460972 Hom.: 150640 Cov.: 92 AF XY: 0.450 AC XY: 327331 AN XY: 726796

African (AFR) AF: 0.118 AC: 3949 AN: 33478

American (AMR) AF: 0.487 AC: 21771 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 13029 AN: 26128

East Asian (EAS) AF: 0.488 AC: 19358 AN: 39692

South Asian (SAS) AF: 0.401 AC: 34585 AN: 86248

European-Finnish (FIN) AF: 0.444 AC: 23420 AN: 52772

Middle Eastern (MID) AF: 0.497 AC: 2868 AN: 5766

European-Non Finnish (NFE) AF: 0.460 AC: 511909 AN: 1111814

Other (OTH) AF: 0.439 AC: 26497 AN: 60378

GnomAD4 genome AF: 0.362 AC: 55135 AN: 152168 Hom.: 11706 Cov.: 34 AF XY: 0.362 AC XY: 26942 AN XY: 74372

African (AFR) AF: 0.128 AC: 5296 AN: 41530

American (AMR) AF: 0.449 AC: 6871 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1763 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2428 AN: 5174

South Asian (SAS) AF: 0.405 AC: 1954 AN: 4828

European-Finnish (FIN) AF: 0.423 AC: 4481 AN: 10582

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31050 AN: 67964

Other (OTH) AF: 0.415 AC: 878 AN: 2114

Alfa AF: 0.383 Hom.: 5708

Bravo AF: 0.356

Asia WGS AF: 0.443 AC: 1536 AN: 3478

EpiCase AF: 0.473

EpiControl AF: 0.483

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

CELSR2-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	2.4
DANN	Benign	0.83
PhyloP100		-6.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6698843; hg19: chr1-109806834; COSMIC: COSV54771859; COSMIC: COSV54771859;