NM_005883.3:c.204G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005883.3(APC2):c.204G>A(p.Gly68Gly) 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

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

cortical dysplasia, complex, with other brain malformations 10
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
lissencephaly spectrum disorders
Inheritance: AR Classification: STRONG Submitted by: ClinGen
Sotos syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
intellectual developmental disorder, autosomal recessive 74
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

APC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005883.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APC2	NM_005883.3	MANE Select	c.204G>A	p.Gly68Gly	synonymous	Exon 3 of 15	NP_005874.1	O95996-1
	APC2	NM_001351273.1		c.204G>A	p.Gly68Gly	synonymous	Exon 2 of 14	NP_001338202.1	O95996-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APC2	ENST00000590469.6	TSL:1 MANE Select	c.204G>A	p.Gly68Gly	synonymous	Exon 3 of 15	ENSP00000467073.2	O95996-1
APC2	ENST00000233607.6	TSL:1	c.204G>A	p.Gly68Gly	synonymous	Exon 3 of 15	ENSP00000233607.2	O95996-1
APC2	ENST00000535453.5	TSL:1	c.204G>A	p.Gly68Gly	synonymous	Exon 2 of 14	ENSP00000442954.1	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

GnomAD2 exomes

AF:

0.00846

AC:

1807

AN:

213638

AF XY:

0.00736

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 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

African (AFR)

AF:

0.000481

AC:

AN:

33262

American (AMR)

AF:

0.0167

AC:

675

AN:

40312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25676

East Asian (EAS)

AF:

0.0978

AC:

3811

AN:

38950

South Asian (SAS)

AF:

0.00152

AC:

128

AN:

84460

European-Finnish (FIN)

AF:

0.00520

AC:

266

AN:

51140

Middle Eastern (MID)

AF:

0.000872

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.000378

AC:

417

AN:

1102386

Other (OTH)

AF:

0.00404

AC:

241

AN:

59614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

367

734

1101

1468

1835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00424

AC:

646

AN:

152332

Hom.:

Cov.:

AF XY:

0.00503

AC XY:

375

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000794

AC:

AN:

41566

American (AMR)

AF:

0.00947

AC:

145

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0647

AC:

335

AN:

5178

South Asian (SAS)

AF:

0.00331

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00611

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000661

AC:

AN:

68030

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000976

Hom.:

Bravo

AF:

0.00535

Asia WGS

AF:

0.0300

AC:

103

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.5

(source)

DANN

Benign

0.88

PhyloP100

0.16

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over