NM_016580.4:c.3540_3545delCAGCAG

Variant names:

• chr5-141945390-CCTGCTG-C
• rs5871792
• NM_016580.4:c.3540_3545delCAGCAG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016580.4(PCDH12):​c.3540_3545delCAGCAG​(p.Ser1180_Ser1181del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,402,056 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PCDH12 NM_016580.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• Publications: 0 publications found

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]

DELE1 (HGNC:28969): (DAP3 binding cell death enhancer 1) Enables protein kinase binding activity and protein serine/threonine kinase activator activity. Involved in HRI-mediated signaling; extrinsic apoptotic signaling pathway via death domain receptors; and regulation of cysteine-type endopeptidase activity involved in apoptotic process. Located in cytosol and mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016580.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH12	NM_016580.4	MANE Select	c.3540_3545delCAGCAG	p.Ser1180_Ser1181del	disruptive_inframe_deletion	Exon 4 of 4	NP_057664.1	Q9NPG4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH12	ENST00000231484.4	TSL:1 MANE Select	c.3540_3545delCAGCAG	p.Ser1180_Ser1181del	disruptive_inframe_deletion	Exon 4 of 4	ENSP00000231484.3	Q9NPG4
	DELE1	ENST00000895929.1		c.*2-1396_*2-1391delTGCTGC		intron	N/A	ENSP00000565988.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1402056 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 697228

African (AFR) AF: 0.00 AC: 0 AN: 33098

American (AMR) AF: 0.00 AC: 0 AN: 42656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 37418

South Asian (SAS) AF: 0.00 AC: 0 AN: 82742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5602

European-Non Finnish (NFE) AF: 9.37e-7 AC: 1 AN: 1067034

Other (OTH) AF: 0.00 AC: 0 AN: 58240

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2

Splicing

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

Other links and lift over

dbSNP: rs5871792; hg19: chr5-141324955;