rs150560922

Variant names:

• chr9-137175362-C-G
• rs150560922
• NM_013366.4:c.2131G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-137175362-C-G
• chr9-137175362-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G711S) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013366.4. 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
	ANAPC2	NM_013366.4	MANE Select	c.2131G>C	p.Gly711Arg	missense	Exon 12 of 13	NP_037498.1	Q9UJX6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANAPC2	ENST00000323927.3	TSL:1 MANE Select	c.2131G>C	p.Gly711Arg	missense	Exon 12 of 13	ENSP00000314004.2	Q9UJX6-1
	ANAPC2	ENST00000900367.1		c.2197G>C	p.Gly733Arg	missense	Exon 13 of 14	ENSP00000570426.1
	ANAPC2	ENST00000900365.1		c.2188G>C	p.Gly730Arg	missense	Exon 13 of 14	ENSP00000570424.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111550

Other (OTH) AF: 0.00 AC: 0 AN: 60282

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		5.6
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
Mutation Taster		=36/64	disease causing

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

Other links and lift over

dbSNP: rs150560922; hg19: chr9-140069814;