9-137175710-T-C

Position:

• chr9-137175710-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 17/23 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

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19866017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANAPC2	NM_013366.4	c.2018A>G	p.Gln673Arg	missense_variant, splice_region_variant	11/13	ENST00000323927.3
LOC124902315	XR_007061879.1	n.1114T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANAPC2	ENST00000323927.3	c.2018A>G	p.Gln673Arg	missense_variant, splice_region_variant	11/13	1	NM_013366.4	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2022

The c.2018A>G (p.Q673R) alteration is located in exon 11 (coding exon 11) of the ANAPC2 gene. This alteration results from a A to G substitution at nucleotide position 2018, causing the glutamine (Q) at amino acid position 673 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	-0.25	N
MutationTaster	Benign	0.78	D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.074
Sift	Benign	0.031	D
Sift4G	Benign	0.28	T
Polyphen		0.098	B
Vest4		0.26
MutPred		0.43		Gain of phosphorylation at S675 (P = 0.1443);
MVP		0.62
MPC		0.67
ClinPred		0.58	D
GERP RS		3.2
Varity_R		0.23
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-140070162;