1-232984475-G-A

Variant names:

• chr1-232984475-G-A
• rs61741049
• NM_014801.4:c.6243C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014801.4(PCNX2):​c.6243C>T​(p.His2081His) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,611,922 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0091 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (18 hom.)
• Consequence: PCNX2 NM_014801.4 splice_region, synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.551
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-232984475-G-A is Benign according to our data. Variant chr1-232984475-G-A is described in ClinVar as Benign. ClinVar VariationId is 723219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.551 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00912 (1388/152240) while in subpopulation AFR AF = 0.0316 (1311/41538). AF 95% confidence interval is 0.0301. There are 19 homozygotes in GnomAd4. There are 643 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 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.6243C>T	p.His2081His	splice_region synonymous	Exon 34 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.6243C>T	p.His2081His	splice_region synonymous	Exon 34 of 34	ENSP00000258229.8	A6NKB5-1
	PCNX2	ENST00000912675.1		c.5868C>T	p.His1956His	splice_region synonymous	Exon 31 of 31	ENSP00000582734.1
	PCNX2	ENST00000344698.6	TSL:2	c.*1479C>T		3_prime_UTR	Exon 10 of 10	ENSP00000340759.2	A6NKB5-3

Frequencies

GnomAD3 genomes AF: 0.00912 AC: 1388 AN: 152122 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00248 AC: 604 AN: 243728 AF XY: 0.00206

Gnomad AFR exome AF: 0.0345

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000219

Gnomad OTH exome AF: 0.00152

GnomAD4 exome AF: 0.00116 AC: 1692 AN: 1459682 Hom.: 18 Cov.: 31 AF XY: 0.00106 AC XY: 772 AN XY: 726198

African (AFR) AF: 0.0348 AC: 1159 AN: 33338

American (AMR) AF: 0.00135 AC: 60 AN: 44316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26006

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53120

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5754

European-Non Finnish (NFE) AF: 0.000293 AC: 326 AN: 1111156

Other (OTH) AF: 0.00227 AC: 137 AN: 60256

GnomAD4 genome AF: 0.00912 AC: 1388 AN: 152240 Hom.: 19 Cov.: 32 AF XY: 0.00864 AC XY: 643 AN XY: 74448

African (AFR) AF: 0.0316 AC: 1311 AN: 41538

American (AMR) AF: 0.00255 AC: 39 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68010

Other (OTH) AF: 0.00711 AC: 15 AN: 2110

Alfa AF: 0.00428 Hom.: 2

Bravo AF: 0.0102

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

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	-0.82
CADD	Benign	6.4
DANN	Benign	0.39
PhyloP100		0.55
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs61741049; hg19: chr1-233120221;