1-233227227-G-T

Variant names:

• chr1-233227227-G-T
• rs74147307
• NM_014801.4:c.2503C>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_014801.4(PCNX2):​c.2503C>A​(p.Arg835Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,611,262 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (13 hom.)
• Consequence: PCNX2 NM_014801.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0007232
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.14
• Publications: 3 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 1-233227227-G-T is Benign according to our data. Variant chr1-233227227-G-T is described in ClinVar as Benign. ClinVar VariationId is 783967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.14 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00727 (1107/152236) while in subpopulation AFR AF = 0.0253 (1052/41544). AF 95% confidence interval is 0.0241. There are 9 homozygotes in GnomAd4. There are 504 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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.2503C>A	p.Arg835Arg	splice_region synonymous	Exon 10 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.2503C>A	p.Arg835Arg	splice_region synonymous	Exon 10 of 34	ENSP00000258229.8	A6NKB5-1
	PCNX2	ENST00000475463.6	TSL:1	n.649-9043C>A		intron	N/A	ENSP00000429360.1	H0YBF4
	PCNX2	ENST00000912675.1		c.2503C>A	p.Arg835Arg	splice_region synonymous	Exon 10 of 31	ENSP00000582734.1

Frequencies

GnomAD3 genomes AF: 0.00726 AC: 1105 AN: 152118 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00720

GnomAD2 exomes AF: 0.00173 AC: 427 AN: 246542 AF XY: 0.00123

Gnomad AFR exome AF: 0.0251

Gnomad AMR exome AF: 0.000893

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.000843

GnomAD4 exome AF: 0.000752 AC: 1097 AN: 1459026 Hom.: 13 Cov.: 32 AF XY: 0.000661 AC XY: 480 AN XY: 725824

African (AFR) AF: 0.0282 AC: 941 AN: 33386

American (AMR) AF: 0.00104 AC: 46 AN: 44314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.000128 AC: 11 AN: 85732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1110598

Other (OTH) AF: 0.00148 AC: 89 AN: 60258

GnomAD4 genome AF: 0.00727 AC: 1107 AN: 152236 Hom.: 9 Cov.: 32 AF XY: 0.00677 AC XY: 504 AN XY: 74446

African (AFR) AF: 0.0253 AC: 1052 AN: 41544

American (AMR) AF: 0.00209 AC: 32 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68016

Other (OTH) AF: 0.00712 AC: 15 AN: 2106

Alfa AF: 0.00261 Hom.: 6

Bravo AF: 0.00856

Asia WGS AF: 0.00115 AC: 4 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	-0.31
CADD	Benign	10
DANN	Benign	0.67
PhyloP100		1.1
PromoterAI		-0.024	Neutral
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00072
dbscSNV1_RF	Benign	0.10
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

Other links and lift over

dbSNP: rs74147307; hg19: chr1-233362973;