chr9-137175362-C-G

Variant names:

• chr9-137175362-C-G
• NM_013366.4:c.2131G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_013366.4(ANAPC2):​c.2131G>C​(p.Gly711Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ANAPC2 NM_013366.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.62

Genes affected

ANAPC2 (HGNC:19989): (anaphase promoting complex subunit 2) A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition by ubiquitinating its specific substrates such as mitotic cyclins and anaphase inhibitor, which are subsequently degraded by the 26S proteasome. Biochemical studies have shown that the vertebrate APC contains eight subunits. The composition of the APC is highly conserved in organisms from yeast to humans. The product of this gene is a component of the complex and shares sequence similarity with a recently identified family of proteins called cullins, which may also be involved in ubiquitin-mediated degradation. [provided by RefSeq, Jul 2008]

LOC124902315 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANAPC2	NM_013366.4	c.2131G>C	p.Gly711Arg	missense_variant	Exon 12 of 13	ENST00000323927.3	NP_037498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANAPC2	ENST00000323927.3	c.2131G>C	p.Gly711Arg	missense_variant	Exon 12 of 13	1	NM_013366.4	ENSP00000314004.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459430 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 725960

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D
Eigen	Benign	0.17
Eigen_PC	Benign	0.052
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.81	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.052	D
MutationAssessor	Benign	1.8	L
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.55
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.047	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.47		Gain of solvent accessibility (P = 0.019);
MVP		0.87
MPC		1.8
ClinPred		0.94	D
GERP RS		3.4
Varity_R		0.48
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-140069814;