Variant 5-141945390-C-CCTGCTGCTGCTG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_016580.4(PCDH12):c.3534_3545dupCAGCAGCAGCAG(p.Ser1178_Ser1181dup) variant causes a disruptive 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 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.71

Variant links:

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]

PCDH12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
PCDH12	NM_016580.4 linkuse as main transcript	c.3534_3545dupCAGCAGCAGCAG	p.Ser1178_Ser1181dup	disruptive_inframe_insertion	4/4	ENST00000231484.4	NP_057664.1	Q9NPG4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH12	ENST00000231484.4 linkuse as main transcript	c.3534_3545dupCAGCAGCAGCAG	p.Ser1178_Ser1181dup	disruptive_inframe_insertion	4/4	1	NM_016580.4	ENSP00000231484.3		Q9NPG4

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3252

AN:

149104

Hom.:

124

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00227

AC XY:

1586

AN XY:

697204

show subpopulations

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.:

AF XY:

0.0216

AC XY:

1572

AN XY:

72914

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 08, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over