chr19-53906891-TGTAATCTCACCCGCCGCCACTAGGTGTCCCCAACGTCCCCTCCGCCGTGCCGGCGGCAGCCCCACTTCACCCCCAACTTCACCACCCCCTGTCCCATTCTAG-T

Variant names:

• chr19-53906891-TGTAATCTCACCCGCCGCCACTAGGTGTCCCCAACGTCCCCTCCGCCGTGCCGGCGGCAGCCCCACTTCACCCCCAACTTCACCACCCCCTGTCCCATTCTAG-T
• rs1555808841
• NM_002739.5:c.2091_*98del

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM4 PP5

The NM_002739.5(PRKCG):​c.2091_*98del​(p.Met697_Ter698delins???) variant causes a stop lost, conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 30)
• Consequence: PRKCG NM_002739.5 stop_lost, conservative_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 3.56
• Publications: 0 publications found

Genes affected

PRKCG (HGNC:9402): (protein kinase C gamma) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play distinct roles in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase is expressed solely in the brain and spinal cord and its localization is restricted to neurons. It has been demonstrated that several neuronal functions, including long term potentiation (LTP) and long term depression (LTD), specifically require this kinase. Knockout studies in mice also suggest that this kinase may be involved in neuropathic pain development. Defects in this protein have been associated with neurodegenerative disorder spinocerebellar ataxia-14 (SCA14). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

PRKCG Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 14

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM4: Stoplost variant in NM_002739.5 Downstream stopcodon found after 70 codons.
• PP5: Variant 19-53906891-TGTAATCTCACCCGCCGCCACTAGGTGTCCCCAACGTCCCCTCCGCCGTGCCGGCGGCAGCCCCACTTCACCCCCAACTTCACCACCCCCTGTCCCATTCTAG-T is Pathogenic according to our data. Variant chr19-53906891-TGTAATCTCACCCGCCGCCACTAGGTGTCCCCAACGTCCCCTCCGCCGTGCCGGCGGCAGCCCCACTTCACCCCCAACTTCACCACCCCCTGTCCCATTCTAG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 13252.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002739.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCG	NM_002739.5	MANE Select	c.2091_*98del	p.Met697_Ter698delins???	stop_lost conservative_inframe_deletion	Exon 18 of 18	NP_002730.1
	PRKCG	NM_002739.5	MANE Select	c.2091_*98del		3_prime_UTR	Exon 18 of 18	NP_002730.1
	PRKCG	NM_001316329.2		c.2090+1_2091-1del		splice_acceptor splice_donor splice_region intron	N/A	NP_001303258.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCG	ENST00000263431.4	TSL:1 MANE Select	c.2091_*98del	p.Met697_Ter698delins???	stop_lost conservative_inframe_deletion	Exon 18 of 18	ENSP00000263431.3
	PRKCG	ENST00000263431.4	TSL:1 MANE Select	c.2091_*98del		3_prime_UTR	Exon 18 of 18	ENSP00000263431.3
	PRKCG	ENST00000683513.1		c.1983_*98del	p.Met661_Ter662delins???	stop_lost 3_prime_UTR_truncation exon_loss conservative_inframe_deletion splice_region	Exon 17 of 17	ENSP00000506809.1

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Spinocerebellar ataxia type 14 Pathogenic:1 Other:1

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

Oct 01, 2009

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6
Mutation Taster		=22/178	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1555808841; hg19: chr19-54410145;