20-5119640-CC-TG

Variant names:

• chr20-5119640-CC-TG
• NM_182649.2:c.158_159delGGinsCA
• PCNA p.Arg53Pro

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP2

The NM_182649.2(PCNA):​c.158_159delGGinsCA​(p.Arg53Pro) variant causes a missense change involving the alteration of a 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 MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R53Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PCNA NM_182649.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.45
• Publications: 0 publications found

Genes affected

PCNA (HGNC:8729): (proliferating cell nuclear antigen) The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene. Pseudogenes of this gene have been described on chromosome 4 and on the X chromosome. [provided by RefSeq, Jul 2008]

ENSG00000302261 (HGNC:):

PCNA-AS1 (HGNC:37184): (PCNA antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 2.4744 (below the threshold of 3.09). Trascript score misZ: 3.2291 (above the threshold of 3.09). GenCC associations: The gene is linked to hereditary ataxia, ataxia-telangiectasia-like disorder 2.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182649.2. 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
	PCNA	NM_182649.2	MANE Select	c.158_159delGGinsCA	p.Arg53Pro	missense	N/A	NP_872590.1	P12004
	PCNA	NM_002592.2		c.158_159delGGinsCA	p.Arg53Pro	missense	N/A	NP_002583.1	P12004
	PCNA-AS1	NR_028370.1		n.55_56delCCinsTG		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNA	ENST00000379143.10	TSL:1 MANE Select	c.158_159delGGinsCA	p.Arg53Pro	missense	N/A	ENSP00000368438.5	P12004
	PCNA	ENST00000379160.3	TSL:5	c.158_159delGGinsCA	p.Arg53Pro	missense	N/A	ENSP00000368458.3	P12004
	PCNA	ENST00000875657.1		c.158_159delGGinsCA	p.Arg53Pro	missense	N/A	ENSP00000545716.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.4

Splicing

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

hg19: chr20-5100286;