rs2242245

Variant names:

• chr19-53900547-T-C
• rs2242245
• NM_002739.5:c.1437-64T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-53900547-T-C
• chr19-53900547-T-A
• chr19-53900547-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002739.5(PRKCG):​c.1437-64T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,614,186 control chromosomes in the GnomAD database, including 997 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (193 hom., cov: 32)
  • Exomes 𝑓: 0.015 (804 hom.)
• Consequence: PRKCG NM_002739.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.34
• Publications: 11 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 19-53900547-T-C is Benign according to our data. Variant chr19-53900547-T-C is described in ClinVar as Benign. ClinVar VariationId is 1270032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCG	NM_002739.5	MANE Select	c.1437-64T>C		intron	N/A	NP_002730.1	P05129-1
	PRKCG	NM_001316329.2		c.1437-64T>C		intron	N/A	NP_001303258.1	A0A804HIU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCG	ENST00000263431.4	TSL:1 MANE Select	c.1437-64T>C		intron	N/A	ENSP00000263431.3	P05129-1
	PRKCG	ENST00000682028.1		c.1437-64T>C		intron	N/A	ENSP00000507230.1	A0A804HIU5
	PRKCG	ENST00000683513.1		c.1437-64T>C		intron	N/A	ENSP00000506809.1	A0A804HHY0

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 5041 AN: 152204 Hom.: 193 Cov.: 32

Gnomad AFR AF: 0.0786

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0264

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.00282

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00550

Gnomad OTH AF: 0.0330

GnomAD4 exome AF: 0.0151 AC: 22077 AN: 1461864 Hom.: 804 Cov.: 33 AF XY: 0.0153 AC XY: 11126 AN XY: 727238

African (AFR) AF: 0.0786 AC: 2630 AN: 33480

American (AMR) AF: 0.0465 AC: 2079 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00631 AC: 165 AN: 26136

East Asian (EAS) AF: 0.151 AC: 5983 AN: 39700

South Asian (SAS) AF: 0.0419 AC: 3618 AN: 86258

European-Finnish (FIN) AF: 0.00382 AC: 204 AN: 53406

Middle Eastern (MID) AF: 0.0264 AC: 152 AN: 5768

European-Non Finnish (NFE) AF: 0.00533 AC: 5929 AN: 1111996

Other (OTH) AF: 0.0218 AC: 1317 AN: 60396

GnomAD4 genome AF: 0.0332 AC: 5051 AN: 152322 Hom.: 193 Cov.: 32 AF XY: 0.0338 AC XY: 2521 AN XY: 74488

African (AFR) AF: 0.0787 AC: 3273 AN: 41566

American (AMR) AF: 0.0264 AC: 404 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.121 AC: 627 AN: 5178

South Asian (SAS) AF: 0.0503 AC: 243 AN: 4830

European-Finnish (FIN) AF: 0.00282 AC: 30 AN: 10624

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00550 AC: 374 AN: 68034

Other (OTH) AF: 0.0326 AC: 69 AN: 2114

Alfa AF: 0.0213 Hom.: 136

Bravo AF: 0.0375

Asia WGS AF: 0.104 AC: 360 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0050
DANN	Benign	0.29
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2242245;

hg19: chr19-54403801;

COSMIC: COSV54725610;