1-233218184-T-G

Variant names:

• chr1-233218184-T-G
• NM_014801.4:c.2505A>C
• PCNX2 p.Arg835Arg

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_014801.4(PCNX2):​c.2505A>C​(p.Arg835Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R835R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 29)
• Consequence: PCNX2 NM_014801.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001372
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 0 publications found

Genes affected

PCNX2 (HGNC:8736): (pecanex 2) This gene contains coding mononucleotide repeats that are associated with tumors of high mcrosatellite instability (MSI-H). Defects in this gene are involved in the tumorigenesis of MSI-H colorectal carcinomas. [provided by RefSeq, Jun 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=0.186 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014801.4. 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
	PCNX2	NM_014801.4	MANE Select	c.2505A>C	p.Arg835Arg	splice_region synonymous	Exon 11 of 34	NP_055616.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNX2	ENST00000258229.14	TSL:5 MANE Select	c.2505A>C	p.Arg835Arg	splice_region synonymous	Exon 11 of 34	ENSP00000258229.8	A6NKB5-1
	PCNX2	ENST00000475463.6	TSL:1	n.649A>C		splice_region non_coding_transcript_exon	Exon 6 of 17	ENSP00000429360.1	H0YBF4
	PCNX2	ENST00000912675.1		c.2505A>C	p.Arg835Arg	splice_region synonymous	Exon 11 of 31	ENSP00000582734.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	8.3
DANN	Benign	0.21
PhyloP100		0.19
PromoterAI		0.00040	Neutral
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.13
SpliceAI score (max)		0.030		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

hg19: chr1-233353930;