Genetic Variant PCDH12:p.Ser1181_Arg1182insSerSerSerSerSerSerSer (chr5-141945390-C-CCTGCTGCTGCTGCTGCTGCTG) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The NM_016580.4(PCDH12):c.3545_3546insCAGCAGCAGCAGCAGCAGCAG(p.Ser1181_Arg1182insSerSerSerSerSerSerSer) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,551,174 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000094 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

PCDH12
NM_016580.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000939 (14/149116) while in subpopulation AMR AF= 0.000796 (12/15080). AF 95% confidence interval is 0.000459. There are 1 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH12	NM_016580.4 link	c.3545_3546insCAGCAGCAGCAGCAGCAGCAG	p.Ser1181_Arg1182insSerSerSerSerSerSerSer	disruptive_inframe_insertion	Exon 4 of 4	ENST00000231484.4	NP_057664.1	Q9NPG4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH12	ENST00000231484.4 link	c.3545_3546insCAGCAGCAGCAGCAGCAGCAG	p.Ser1181_Arg1182insSerSerSerSerSerSerSer	disruptive_inframe_insertion	Exon 4 of 4	1	NM_016580.4	ENSP00000231484.3		Q9NPG4

Frequencies

GnomAD3 genomes

AF:

0.0000939

AC:

AN:

149116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000796

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000970

GnomAD4 exome

AF:

0.00000499

AC:

AN:

1402058

Hom.:

Cov.:

AF XY:

0.00000861

AC XY:

AN XY:

697228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000187

Gnomad4 OTH exome

AF:

0.0000859

GnomAD4 genome

AF:

0.0000939

AC:

AN:

149116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72794

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000796

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000970

ClinVar

Not reported in ClinVar

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over