Variant 1-17438419-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_018715.4(RCC2):c.96G>A(p.Ala32=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00764 in 1,273,264 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0080 ( 49 hom. )

Consequence

RCC2
NM_018715.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.467

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 1-17438419-C-T is Benign according to our data. Variant chr1-17438419-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638396.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.467 with no splicing effect.

BS2

High AC in GnomAd4 at 747 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCC2	NM_018715.4 linkuse as main transcript	c.96G>A	p.Ala32=	synonymous_variant	2/13	ENST00000375436.9	NP_061185.1
RCC2	NM_001136204.3 linkuse as main transcript	c.96G>A	p.Ala32=	synonymous_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.96G>A	p.Ala32=	synonymous_variant	2/13	1	NM_018715.4	ENSP00000364585	P1
RCC2	ENST00000375433.3 linkuse as main transcript	c.96G>A	p.Ala32=	synonymous_variant	1/12	1		ENSP00000364582	P1

Frequencies

GnomAD3 genomes

AF:

0.00493

AC:

747

AN:

151606

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.0374

Gnomad AMR

AF:

0.00420

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.00230

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00719

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.0149

AC:

AN:

3688

Hom.:

AF XY:

0.0144

AC XY:

AN XY:

2364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00714

Gnomad ASJ exome

AF:

0.0385

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0144

Gnomad FIN exome

AF:

0.00862

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.00800

AC:

8977

AN:

1121552

Hom.:

Cov.:

AF XY:

0.00815

AC XY:

4391

AN XY:

538670

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00326

Gnomad4 ASJ exome

AF:

0.00643

Gnomad4 EAS exome

AF:

0.0000379

Gnomad4 SAS exome

AF:

0.00515

Gnomad4 FIN exome

AF:

0.00468

Gnomad4 NFE exome

AF:

0.00865

Gnomad4 OTH exome

AF:

0.00792

GnomAD4 genome

AF:

0.00492

AC:

747

AN:

151712

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

319

AN XY:

74140

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00420

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.00230

Gnomad4 NFE

AF:

0.00719

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00466

Hom.:

Bravo

AF:

0.00491

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

RCC2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over