9-137180318-C-T

Variant names:

• chr9-137180318-C-T
• NM_013366.4:c.1753G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013366.4(ANAPC2):​c.1753G>A​(p.Glu585Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,912 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANAPC2 NM_013366.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.25

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANAPC2	NM_013366.4	c.1753G>A	p.Glu585Lys	missense_variant	Exon 10 of 13	ENST00000323927.3	NP_037498.1
ANAPC2	XM_047423274.1	c.1753G>A	p.Glu585Lys	missense_variant	Exon 10 of 13		XP_047279230.1
ANAPC2	XM_047423275.1	c.1753G>A	p.Glu585Lys	missense_variant	Exon 10 of 12		XP_047279231.1
ANAPC2	XM_047423276.1	c.1753G>A	p.Glu585Lys	missense_variant	Exon 10 of 13		XP_047279232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANAPC2	ENST00000323927.3	c.1753G>A	p.Glu585Lys	missense_variant	Exon 10 of 13	1	NM_013366.4	ENSP00000314004.2
ANAPC2	ENST00000483432.1	n.93G>A		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460912 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726728

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: 0.00000180

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	Benign	0.11
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.22
Sift	Benign	0.080	T
Sift4G	Benign	0.088	T
Polyphen		0.055	B
Vest4		0.65
MutPred		0.38		Gain of ubiquitination at E585 (P = 0.006);
MVP		0.80
MPC		0.72
ClinPred		0.67	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.36

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-140074770;