Variant 1-17438469-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_018715.4(RCC2):c.46T>G(p.Ser16Ala) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RCC2
NM_018715.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

Variant links:

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]

RCC2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity RCC2_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10631895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCC2	NM_018715.4 linkuse as main transcript	c.46T>G	p.Ser16Ala	missense_variant	2/13	ENST00000375436.9	NP_061185.1
RCC2	NM_001136204.3 linkuse as main transcript	c.46T>G	p.Ser16Ala	missense_variant	1/12		NP_001129676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCC2	ENST00000375436.9 linkuse as main transcript	c.46T>G	p.Ser16Ala	missense_variant	2/13	1	NM_018715.4	ENSP00000364585	P1
RCC2	ENST00000375433.3 linkuse as main transcript	c.46T>G	p.Ser16Ala	missense_variant	1/12	1		ENSP00000364582	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1180906

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

573650

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2021

The c.46T>G (p.S16A) alteration is located in exon 2 (coding exon 1) of the RCC2 gene. This alteration results from a T to G substitution at nucleotide position 46, causing the serine (S) at amino acid position 16 to be replaced by an alanine (A). 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

0.076

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.30

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

0.91

N;N

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.042

Sift

Benign

0.42

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0080

B;B

Vest4

0.16

MutPred

0.21

Loss of glycosylation at S16 (P = 0.0018);Loss of glycosylation at S16 (P = 0.0018);

MVP

0.24

MPC

0.89

ClinPred

0.070

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.20

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over