rs2800687

Positions:

• chr1-17437021-A-G
• chr1-17437021-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018715.4(RCC2):​c.285+1209T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,146 control chromosomes in the GnomAD database, including 33,074 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33074 hom., cov: 33)
• Consequence: RCC2 NM_018715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCC2	NM_018715.4	c.285+1209T>C		intron_variant		ENST00000375436.9	NP_061185.1
RCC2	NM_001136204.3	c.285+1209T>C		intron_variant			NP_001129676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCC2	ENST00000375436.9	c.285+1209T>C		intron_variant		1	NM_018715.4	ENSP00000364585.4
RCC2	ENST00000375433.3	c.285+1209T>C		intron_variant		1		ENSP00000364582.3

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99893 AN: 152028 Hom.: 33051 Cov.: 33

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.642

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.657 AC: 99975 AN: 152146 Hom.: 33074 Cov.: 33 AF XY: 0.657 AC XY: 48876 AN XY: 74392

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.644

Alfa AF: 0.647 Hom.: 16032

Bravo AF: 0.664

Asia WGS AF: 0.643 AC: 2238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.55

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

LitVar

Other links and lift over

dbSNP: rs2800687; hg19: chr1-17763517;