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GeneBe

1-17438419-C-T

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

1
1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.467 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 747 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RCC2NM_018715.4 linkuse as main transcriptc.96G>A p.Ala32= synonymous_variant 2/13 ENST00000375436.9
RCC2NM_001136204.3 linkuse as main transcriptc.96G>A p.Ala32= synonymous_variant 1/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RCC2ENST00000375436.9 linkuse as main transcriptc.96G>A p.Ala32= synonymous_variant 2/131 NM_018715.4 P1
RCC2ENST00000375433.3 linkuse as main transcriptc.96G>A p.Ala32= synonymous_variant 1/121 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00493
AC:
747
AN:
151606
Hom.:
1
Cov.:
32
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:
55
AN:
3688
Hom.:
2
AF XY:
0.0144
AC XY:
34
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.:
49
Cov.:
30
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00492
AC:
747
AN:
151712
Hom.:
1
Cov.:
32
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.:
0
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenSep 01, 2022RCC2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
Cadd
Benign
12
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.

Other links and lift over

dbSNP: rs527576288; hg19: chr1-17764915; API