1-233017164-A-AAAAGCAAGATTTTGAGTCCTCACAGCTATTCT

Position:

• chr1-233017164-A-AAAAGCAAGATTTTGAGTCCTCACAGCTATTCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014801.4(PCNX2):​c.4606-11_4606-10insAGAATAGCTGTGAGGACTCAAAATCTTGCTTT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,392,556 control chromosomes in the GnomAD database, including 90,592 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14805 hom., cov: 22)
  • Exomes 𝑓: 0.35 (90592 hom.)
  • Failed GnomAD Quality Control
• Consequence: PCNX2 NM_014801.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.581

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-233017164-A-AAAAGCAAGATTTTGAGTCCTCACAGCTATTCT is Benign according to our data. Variant chr1-233017164-A-AAAAGCAAGATTTTGAGTCCTCACAGCTATTCT is described in ClinVar as [Benign]. Clinvar id is 2975927.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCNX2	NM_014801.4	c.4606-11_4606-10insAGAATAGCTGTGAGGACTCAAAATCTTGCTTT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000258229.14	NP_055616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNX2	ENST00000258229.14	c.4606-11_4606-10insAGAATAGCTGTGAGGACTCAAAATCTTGCTTT		splice_polypyrimidine_tract_variant, intron_variant		5	NM_014801.4	ENSP00000258229	A2
PCNX2	ENST00000344698.6	c.562-11_562-10insAGAATAGCTGTGAGGACTCAAAATCTTGCTTT		splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000340759	P4
PCNX2	ENST00000462233.5	c.1416-11_1416-10insAGAATAGCTGTGAGGACTCAAAATCTTGCTTT		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		2		ENSP00000428488
PCNX2	ENST00000522067.1	n.488-11_488-10insAGAATAGCTGTGAGGACTCAAAATCTTGCTTT		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64670 AN: 151338 Hom.: 14782 Cov.: 22

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.423

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.439

GnomAD4 exome AF: 0.352 AC: 489728 AN: 1392556 Hom.: 90592 Cov.: 32 AF XY: 0.349 AC XY: 239735 AN XY: 687096

Gnomad4 AFR exome AF: 0.605

Gnomad4 AMR exome AF: 0.457

Gnomad4 ASJ exome AF: 0.367

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.314

Gnomad4 NFE exome AF: 0.338

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.427 AC: 64746 AN: 151458 Hom.: 14805 Cov.: 22 AF XY: 0.426 AC XY: 31480 AN XY: 73978

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.440

Alfa AF: 0.317 Hom.: 1305

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 05, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11271054; hg19: chr1-233152910;