chr19-1450086-C-T

Position:

• chr19-1450086-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000587869.5(APC2):​c.-18-2898C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00781 in 960,586 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0056 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0082 (26 hom.)
• Consequence: APC2 ENST00000587869.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.146

Genes affected

APC2 (HGNC:24036): (APC regulator of WNT signaling pathway 2) This gene encodes a strongly conserved protein that has an N-terminal coiled-coil domain followed by an armadillo domain, five 20-amino acid repeats, and two SAMP domains. This protein promotes the assembly of a multiprotein complex that recruits and phosphorylates the Wnt effector beta-catenin and targets beta-catenin for ubiquitylation and proteasomal degradation. This protein therefore plays a role in the reduction of cytoplasmic levels of beta-catenin which in turn reduces activation of Wnt target genes that play a pivotal role in the pathogenesis of various human cancers. The protein encoded by this gene is closely related to the adenomatous polyposis coli (APC) tumor-suppressor protein and has similar tumor-suppressor effects. This gene also plays a role in actin assembly, cell-cell adhesion, and microtubule network formation through its interaction with cytoskeletal proteins. This gene has its highest expression in the central nervous system and is involved in brain development through cytoskeletal regulation in neurons. Alternative splicing produces multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-1450086-C-T is Benign according to our data. Variant chr19-1450086-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2648922.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC2	NM_005883.3			upstream_gene_variant		ENST00000590469.6	NP_005874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APC2	ENST00000587869.5	c.-18-2898C>T		intron_variant		5		ENSP00000466803
APC2	ENST00000590469.6			upstream_gene_variant		1	NM_005883.3	ENSP00000467073	P1

Frequencies

GnomAD3 genomes AF: 0.00560 AC: 852 AN: 152028 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.00798

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00889

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.00823 AC: 6651 AN: 808450 Hom.: 26 AF XY: 0.00813 AC XY: 3040 AN XY: 373998

Gnomad4 AFR exome AF: 0.000593

Gnomad4 AMR exome AF: 0.00530

Gnomad4 ASJ exome AF: 0.00240

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00113

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00870

Gnomad4 OTH exome AF: 0.00617

GnomAD4 genome AF: 0.00559 AC: 850 AN: 152136 Hom.: 4 Cov.: 33 AF XY: 0.00531 AC XY: 395 AN XY: 74378

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00791

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00255

Gnomad4 NFE AF: 0.00889

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.00646 Hom.: 1

Bravo AF: 0.00568

Asia WGS AF: 0.000289 AC: 1 AN: 3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

APC2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.9
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs113534259; hg19: chr19-1450085;