1-109250113-A-ACGC

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BA1

The NM_001408.3(CELSR2):c.47_49dup(p.Pro16dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,512,846 control chromosomes in the GnomAD database, including 343,325 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (31205 hom., cov: 0)
  • Exomes 𝑓: 0.68 (312120 hom.)
• Consequence: CELSR2 NM_001408.3 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00700

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 -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001408.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 1-109250113-A-ACGC is Benign according to our data. Variant chr1-109250113-A-ACGC is described in ClinVar as [Benign]. Clinvar id is 767684.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELSR2	NM_001408.3	c.47_49dup	p.Pro16dup	inframe_insertion	1/34	ENST00000271332.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELSR2	ENST00000271332.4	c.47_49dup	p.Pro16dup	inframe_insertion	1/34	1	NM_001408.3	P1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 95904 AN: 150714 Hom.: 31199 Cov.: 0

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.682

GnomAD3 exomes AF: 0.638 AC: 109673 AN: 171874 Hom.: 34708 AF XY: 0.642 AC XY: 62857 AN XY: 97928

Gnomad AFR exome AF: 0.452

Gnomad AMR exome AF: 0.611

Gnomad ASJ exome AF: 0.717

Gnomad EAS exome AF: 0.501

Gnomad SAS exome AF: 0.607

Gnomad FIN exome AF: 0.655

Gnomad NFE exome AF: 0.690

Gnomad OTH exome AF: 0.671

GnomAD4 exome AF: 0.680 AC: 926789 AN: 1362022 Hom.: 312120 Cov.: 60 AF XY: 0.679 AC XY: 459696 AN XY: 676698

Gnomad4 AFR exome AF: 0.479

Gnomad4 AMR exome AF: 0.605

Gnomad4 ASJ exome AF: 0.730

Gnomad4 EAS exome AF: 0.545

Gnomad4 SAS exome AF: 0.614

Gnomad4 FIN exome AF: 0.661

Gnomad4 NFE exome AF: 0.698

Gnomad4 OTH exome AF: 0.670

GnomAD4 genome AF: 0.636 AC: 95950 AN: 150824 Hom.: 31205 Cov.: 0 AF XY: 0.633 AC XY: 46626 AN XY: 73644

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.630

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.683

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs59201433; hg19: chr1-109792735;