chr1-17425618-C-T

Variant names:

• chr1-17425618-C-T
• rs749301831
• NM_018715.4:c.446G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018715.4(RCC2):​c.446G>A​(p.Arg149Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000116 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: RCC2 NM_018715.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04844889).
• BS2: High AC in GnomAd4 at 13 AD gene.

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.446G>A	p.Arg149Gln	missense	Exon 4 of 13	NP_061185.1	A0A024RAC5
	RCC2	NM_001136204.3		c.446G>A	p.Arg149Gln	missense	Exon 3 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.446G>A	p.Arg149Gln	missense	Exon 4 of 13	ENSP00000364585.4	Q9P258
	RCC2	ENST00000375433.3	TSL:1	c.446G>A	p.Arg149Gln	missense	Exon 3 of 12	ENSP00000364582.3	Q9P258
	RCC2	ENST00000927104.1		c.446G>A	p.Arg149Gln	missense	Exon 3 of 12	ENSP00000597163.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000120 AC: 30 AN: 250620 AF XY: 0.000125

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000119 AC: 174 AN: 1461812 Hom.: 0 Cov.: 32 AF XY: 0.0000908 AC XY: 66 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000147 AC: 164 AN: 1111976

Other (OTH) AF: 0.0000662 AC: 4 AN: 60392

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74326

African (AFR) AF: 0.0000241 AC: 1 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000920 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.000165 AC: 20

EpiCase AF: 0.000218

EpiControl AF: 0.000119

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	Benign	0.072
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.62
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.054
FATHMM_MKL	Benign	0.74	D
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.33	N
PhyloP100		5.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.11
Sift	Benign	0.56	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.15
MVP		0.15
MPC		0.98
ClinPred		0.10	T
GERP RS		4.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.8
Varity_R		0.19
gMVP		0.31
Mutation Taster		=78/22	polymorphism

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: rs749301831; hg19: chr1-17752114;