Variant 19-1453309-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005883.3(APC2):c.204G>A(p.Gly68=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,593,864 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 16 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 235 hom. )

Consequence

APC2
NM_005883.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.160

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 19-1453309-G-A is Benign according to our data. Variant chr19-1453309-G-A is described in ClinVar as [Benign]. Clinvar id is 1621323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.059 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.204G>A	p.Gly68=	synonymous_variant	3/15	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.204G>A	p.Gly68=	synonymous_variant	3/15	1	NM_005883.3	ENSP00000467073	P1	O95996-1

Frequencies

GnomAD3 genomes

AF:

0.00424

AC:

645

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00948

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0644

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00611

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00846

AC:

1807

AN:

213638

Hom.:

AF XY:

0.00736

AC XY:

852

AN XY:

115704

show subpopulations

Gnomad AFR exome

AF:

0.000619

Gnomad AMR exome

AF:

0.0175

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0664

Gnomad SAS exome

AF:

0.00159

Gnomad FIN exome

AF:

0.00613

Gnomad NFE exome

AF:

0.000565

Gnomad OTH exome

AF:

0.00483

GnomAD4 exome

AF:

0.00386

AC:

5559

AN:

1441532

Hom.:

235

Cov.:

AF XY:

0.00375

AC XY:

2680

AN XY:

715422

show subpopulations

Gnomad4 AFR exome

AF:

0.000481

Gnomad4 AMR exome

AF:

0.0167

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0978

Gnomad4 SAS exome

AF:

0.00152

Gnomad4 FIN exome

AF:

0.00520

Gnomad4 NFE exome

AF:

0.000378

Gnomad4 OTH exome

AF:

0.00404

GnomAD4 genome

AF:

0.00424

AC:

646

AN:

152332

Hom.:

Cov.:

AF XY:

0.00503

AC XY:

375

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00947

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0647

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.00611

Gnomad4 NFE

AF:

0.000661

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000976

Hom.:

Bravo

AF:

0.00535

Asia WGS

AF:

0.0300

AC:

103

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	Jan 12, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.5

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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