5-141945390-C-CCTGCTG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_016580.4(PCDH12):c.3545_3546insCAGCAG(p.Ser1180_Ser1181dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,447,016 control chromosomes in the GnomAD database, including 23 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (15 hom., cov: 0)
  • Exomes 𝑓: 0.0017 (8 hom.)
• Consequence: PCDH12 NM_016580.4 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 5-141945390-C-CCTGCTG is Benign according to our data. Variant chr5-141945390-C-CCTGCTG is described in ClinVar as [Benign]. Clinvar id is 769662.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00762 (1137/149138) while in subpopulation AFR AF= 0.0264 (1090/41230). AF 95% confidence interval is 0.0251. There are 15 homozygotes in gnomad4. There are 513 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH12	NM_016580.4	c.3545_3546insCAGCAG	p.Ser1180_Ser1181dup	inframe_insertion	4/4	ENST00000231484.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH12	ENST00000231484.4	c.3545_3546insCAGCAG	p.Ser1180_Ser1181dup	inframe_insertion	4/4	1	NM_016580.4	P1

Frequencies

GnomAD3 genomes AF: 0.00762 AC: 1135 AN: 149024 Hom.: 15 Cov.: 0

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00186

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000631

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000151

Gnomad OTH AF: 0.00292

GnomAD4 exome AF: 0.00166 AC: 2158 AN: 1297878 Hom.: 8 Cov.: 59 AF XY: 0.00164 AC XY: 1055 AN XY: 643070

Gnomad4 AFR exome AF: 0.0276

Gnomad4 AMR exome AF: 0.00668

Gnomad4 ASJ exome AF: 0.00150

Gnomad4 EAS exome AF: 0.00294

Gnomad4 SAS exome AF: 0.00248

Gnomad4 FIN exome AF: 0.000918

Gnomad4 NFE exome AF: 0.000562

Gnomad4 OTH exome AF: 0.00244

GnomAD4 genome AF: 0.00762 AC: 1137 AN: 149138 Hom.: 15 Cov.: 0 AF XY: 0.00704 AC XY: 513 AN XY: 72862

Gnomad4 AFR AF: 0.0264

Gnomad4 AMR AF: 0.00186

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000631

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000151

Gnomad4 OTH AF: 0.00288

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: rs5871792; hg19: chr5-141324955;