NM_018715.4:c.1048C>G

Variant names:

• chr1-17413696-G-C
• rs772968944
• NM_018715.4:c.1048C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018715.4(RCC2):​c.1048C>G​(p.Arg350Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RCC2 NM_018715.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.99
• Publications: 0 publications found

Genes affected

RCC2 (HGNC:30297): (regulator of chromosome condensation 2) The protein encoded by this gene is a guanine exchange factor that is active on RalA, a small GTPase. The encoded protein and RalA are both essential for proper kinetochore-microtubule function in early mitosis. This protein has been shown to be a biomarker for colorectal cancer. [provided by RefSeq, Oct 2016]

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, 0.854

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018715.4. 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
	RCC2	NM_018715.4	MANE Select	c.1048C>G	p.Arg350Gly	missense	Exon 9 of 13	NP_061185.1	A0A024RAC5
	RCC2	NM_001136204.3		c.1048C>G	p.Arg350Gly	missense	Exon 8 of 12	NP_001129676.1	Q9P258

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCC2	ENST00000375436.9	TSL:1 MANE Select	c.1048C>G	p.Arg350Gly	missense	Exon 9 of 13	ENSP00000364585.4	Q9P258
	RCC2	ENST00000375433.3	TSL:1	c.1048C>G	p.Arg350Gly	missense	Exon 8 of 12	ENSP00000364582.3	Q9P258
	RCC2	ENST00000927104.1		c.1048C>G	p.Arg350Gly	missense	Exon 8 of 12	ENSP00000597163.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		8.0
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-5.0	D
REVEL	Pathogenic	0.86
Sift	Benign	0.056	T
Sift4G	Benign	0.069	T
Polyphen		1.0	D
Vest4		0.91
MutPred		0.50		Loss of MoRF binding (P = 0.0186)
MVP		0.86
MPC		2.2
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.82
gMVP		0.85
Mutation Taster		=25/75	disease causing

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

Other links and lift over

dbSNP: rs772968944; hg19: chr1-17740192;