chr19-1462052-C-T

Variant names:

• chr19-1462052-C-T
• rs148957868
• NM_005883.3:c.1728C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_005883.3(APC2):​c.1728C>T​(p.Gly576Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,613,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: APC2 NM_005883.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.32
• Publications: 0 publications found

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]

C19orf25 (HGNC:26711): (chromosome 19 open reading frame 25)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 19-1462052-C-T is Benign according to our data. Variant chr19-1462052-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 708468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.32 with no splicing effect.

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.1728C>T	p.Gly576Gly	synonymous	Exon 14 of 15	NP_005874.1	O95996-1
	APC2	NM_001351273.1		c.1725C>T	p.Gly575Gly	synonymous	Exon 13 of 14	NP_001338202.1	O95996-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APC2	ENST00000590469.6	TSL:1 MANE Select	c.1728C>T	p.Gly576Gly	synonymous	Exon 14 of 15	ENSP00000467073.2	O95996-1
	APC2	ENST00000233607.6	TSL:1	c.1728C>T	p.Gly576Gly	synonymous	Exon 14 of 15	ENSP00000233607.2	O95996-1
	APC2	ENST00000535453.5	TSL:1	c.1728C>T	p.Gly576Gly	synonymous	Exon 13 of 14	ENSP00000442954.1	O95996-1

Frequencies

GnomAD3 genomes AF: 0.000388 AC: 59 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000200 AC: 50 AN: 250466 AF XY: 0.000214

Gnomad AFR exome AF: 0.000557

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000354

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000376 AC: 550 AN: 1460866 Hom.: 0 Cov.: 39 AF XY: 0.000355 AC XY: 258 AN XY: 726724

African (AFR) AF: 0.000329 AC: 11 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000462 AC: 514 AN: 1111990

Other (OTH) AF: 0.000381 AC: 23 AN: 60384

GnomAD4 genome AF: 0.000387 AC: 59 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74454

African (AFR) AF: 0.000650 AC: 27 AN: 41556

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000479 Hom.: 0

Bravo AF: 0.000423

EpiCase AF: 0.000382

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.2
DANN	Benign	0.86
PhyloP100		-6.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs148957868; hg19: chr19-1462051;