5-141945390-C-CCTGCTGCTGCTG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_016580.4(PCDH12):c.3545_3546insCAGCAGCAGCAG(p.Ser1178_Ser1181dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00436 in 1,551,240 control chromosomes in the GnomAD database, including 182 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (124 hom., cov: 0)
  • Exomes 𝑓: 0.0025 (58 hom.)
• Consequence: PCDH12 NM_016580.4 inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.71

Genes affected

PCDH12 (HGNC:8657): (protocadherin 12) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 6 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene localizes to the region on chromosome 5 where the protocadherin gene clusters reside. The exon organization of this transcript is similar to that of the gene cluster transcripts, notably the first large exon, but no significant sequence homology exists. The function of this cellular adhesion protein is undetermined but mouse protocadherin 12 does not bind catenins and appears to have no affect on cell migration or growth. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 5-141945390-C-CCTGCTGCTGCTG is Benign according to our data. Variant chr5-141945390-C-CCTGCTGCTGCTG is described in ClinVar as [Benign]. Clinvar id is 1164145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH12	NM_016580.4	c.3545_3546insCAGCAGCAGCAG	p.Ser1178_Ser1181dup	inframe_insertion	4/4	ENST00000231484.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH12	ENST00000231484.4	c.3545_3546insCAGCAGCAGCAG	p.Ser1178_Ser1181dup	inframe_insertion	4/4	1	NM_016580.4	P1

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3252 AN: 149104 Hom.: 124 Cov.: 0

Gnomad AFR AF: 0.0748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00623

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000789

Gnomad SAS AF: 0.00316

Gnomad FIN AF: 0.000295

Gnomad MID AF: 0.00980

Gnomad NFE AF: 0.000302

Gnomad OTH AF: 0.0175

GnomAD4 exome AF: 0.00249 AC: 3489 AN: 1402022 Hom.: 58 Cov.: 59 AF XY: 0.00227 AC XY: 1586 AN XY: 697204

Gnomad4 AFR exome AF: 0.0736

Gnomad4 AMR exome AF: 0.00382

Gnomad4 ASJ exome AF: 0.0000397

Gnomad4 EAS exome AF: 0.000775

Gnomad4 SAS exome AF: 0.00228

Gnomad4 FIN exome AF: 0.000399

Gnomad4 NFE exome AF: 0.000327

Gnomad4 OTH exome AF: 0.00477

GnomAD4 genome AF: 0.0219 AC: 3268 AN: 149218 Hom.: 124 Cov.: 0 AF XY: 0.0216 AC XY: 1572 AN XY: 72914

Gnomad4 AFR AF: 0.0750

Gnomad4 AMR AF: 0.00623

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000791

Gnomad4 SAS AF: 0.00316

Gnomad4 FIN AF: 0.000295

Gnomad4 NFE AF: 0.000302

Gnomad4 OTH AF: 0.0173

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 26, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 08, 2021	- -

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: rs5871792; hg19: chr5-141324955;