Genetic Variant NM_013366.4:c.2018A>G (chr9-137175710-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013366.4(ANAPC2):c.2018A>G(p.Gln673Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Consequence

ANAPC2
NM_013366.4 missense, splice_region

Scores

Splicing: ADA: 0.0007732

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06

Publications

0 publications found

Variant links:

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]

ANAPC2 links:

LOC124902315 (HGNC:):

LOC124902315 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19866017).

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.2018A>G	p.Gln673Arg	missense splice_region	Exon 11 of 13	NP_037498.1	Q9UJX6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANAPC2	ENST00000323927.3	TSL:1 MANE Select	c.2018A>G	p.Gln673Arg	missense splice_region	Exon 11 of 13	ENSP00000314004.2	Q9UJX6-1
ANAPC2	ENST00000900367.1		c.2084A>G	p.Gln695Arg	missense splice_region	Exon 12 of 14	ENSP00000570426.1
ANAPC2	ENST00000900365.1		c.2075A>G	p.Gln692Arg	missense splice_region	Exon 12 of 14	ENSP00000570424.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.43

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.80

M_CAP

Benign

0.053

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.84

MutationAssessor

Benign

-0.25

PhyloP100

2.1

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.0

REVEL

Benign

0.074

Sift

Benign

0.031

Sift4G

Benign

0.28

Polyphen

0.098

Vest4

0.26

MutPred

0.43

Gain of phosphorylation at S675 (P = 0.1443)

MVP

0.62

MPC

0.67

ClinPred

0.58

GERP RS

3.2

Varity_R

0.23

gMVP

0.12

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00077

dbscSNV1_RF

Benign

0.028

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over