chr19-1453161-G-A

Variant names:

• chr19-1453161-G-A
• rs73516808
• NM_005883.3:c.141+19G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005883.3(APC2):​c.141+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,591,302 control chromosomes in the GnomAD database, including 2,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (1150 hom., cov: 33)
  • Exomes 𝑓: 0.0072 (1047 hom.)
• Consequence: APC2 NM_005883.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.192

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-1453161-G-A is Benign according to our data. Variant chr19-1453161-G-A is described in ClinVar as [Benign]. Clinvar id is 1599767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APC2	NM_005883.3	c.141+19G>A		intron_variant	Intron 2 of 14	ENST00000590469.6	NP_005874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APC2	ENST00000590469.6	c.141+19G>A		intron_variant	Intron 2 of 14	1	NM_005883.3	ENSP00000467073.2

Frequencies

GnomAD3 genomes AF: 0.0678 AC: 10308 AN: 152134 Hom.: 1141 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.0440

GnomAD2 exomes AF: 0.0169 AC: 3534 AN: 208608 AF XY: 0.0122

Gnomad AFR exome AF: 0.239

Gnomad AMR exome AF: 0.0131

Gnomad ASJ exome AF: 0.00152

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000280

Gnomad NFE exome AF: 0.00110

Gnomad OTH exome AF: 0.00926

GnomAD4 exome AF: 0.00716 AC: 10302 AN: 1439050 Hom.: 1047 Cov.: 32 AF XY: 0.00621 AC XY: 4434 AN XY: 713838

Gnomad4 AFR exome AF: 0.243 AC: 8019 AN: 32984

Gnomad4 AMR exome AF: 0.0149 AC: 610 AN: 40954

Gnomad4 ASJ exome AF: 0.00132 AC: 34 AN: 25690

Gnomad4 EAS exome AF: 0.0000259 AC: 1 AN: 38572

Gnomad4 SAS exome AF: 0.000503 AC: 42 AN: 83480

Gnomad4 FIN exome AF: 0.000528 AC: 27 AN: 51158

Gnomad4 NFE exome AF: 0.000520 AC: 573 AN: 1101442

Gnomad4 Remaining exome AF: 0.0153 AC: 912 AN: 59520

GnomAD4 genome AF: 0.0680 AC: 10353 AN: 152252 Hom.: 1150 Cov.: 33 AF XY: 0.0672 AC XY: 5002 AN XY: 74446

Gnomad4 AFR AF: 0.235 AC: 0.235379 AN: 0.235379

Gnomad4 AMR AF: 0.0272 AC: 0.0272442 AN: 0.0272442

Gnomad4 ASJ AF: 0.00202 AC: 0.00201845 AN: 0.00201845

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000206954 AN: 0.000206954

Gnomad4 FIN AF: 0.000188 AC: 0.000188324 AN: 0.000188324

Gnomad4 NFE AF: 0.000838 AC: 0.000838112 AN: 0.000838112

Gnomad4 OTH AF: 0.0440 AC: 0.0440341 AN: 0.0440341

Alfa AF: 0.0362 Hom.: 84

Bravo AF: 0.0770

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.84
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs73516808; hg19: chr19-1453160;