Variant chr19-1453161-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.192

Variant links:

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]

APC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
APC2	NM_005883.3 linkuse as main transcript	c.141+19G>A		intron_variant		ENST00000590469.6	NP_005874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APC2	ENST00000590469.6 linkuse as main transcript	c.141+19G>A		intron_variant		1	NM_005883.3	ENSP00000467073	P1	O95996-1

Frequencies

GnomAD3 genomes

AF:

0.0678

AC:

10308

AN:

152134

Hom.:

1141

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0169

AC:

3534

AN:

208608

Hom.:

343

AF XY:

0.0122

AC XY:

1380

AN XY:

112828

show subpopulations

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 SAS exome

AF:

0.000259

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.:

AF XY:

0.00621

AC XY:

4434

AN XY:

713838

show subpopulations

Gnomad4 AFR exome

AF:

0.243

Gnomad4 AMR exome

AF:

0.0149

Gnomad4 ASJ exome

AF:

0.00132

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.000503

Gnomad4 FIN exome

AF:

0.000528

Gnomad4 NFE exome

AF:

0.000520

Gnomad4 OTH exome

AF:

0.0153

GnomAD4 genome

AF:

0.0680

AC:

10353

AN:

152252

Hom.:

1150

Cov.:

AF XY:

0.0672

AC XY:

5002

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.0272

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0362

Hom.:

Bravo

AF:

0.0770

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.7

DANN

Benign

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over