rs527576288

Variant names:

• chr1-17438419-C-T
• rs527576288
• NM_018715.4:c.96G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-17438419-C-T
• chr1-17438419-C-A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_018715.4(RCC2):​c.96G>A​(p.Ala32Ala) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.467
• Publications: 0 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 -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 VariationId 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.

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.96G>A	p.Ala32Ala	synonymous	Exon 2 of 13	NP_061185.1	A0A024RAC5
	RCC2	NM_001136204.3		c.96G>A	p.Ala32Ala	synonymous	Exon 1 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.96G>A	p.Ala32Ala	synonymous	Exon 2 of 13	ENSP00000364585.4	Q9P258
	RCC2	ENST00000375433.3	TSL:1	c.96G>A	p.Ala32Ala	synonymous	Exon 1 of 12	ENSP00000364582.3	Q9P258
	RCC2	ENST00000927104.1		c.96G>A	p.Ala32Ala	synonymous	Exon 1 of 12	ENSP00000597163.1

Frequencies

GnomAD3 genomes AF: 0.00493 AC: 747 AN: 151606 Hom.: 1 Cov.: 32

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

GnomAD2 exomes AF: 0.0149 AC: 55 AN: 3688 AF XY: 0.0144

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 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

African (AFR) AF: 0.00149 AC: 34 AN: 22890

American (AMR) AF: 0.00326 AC: 28 AN: 8602

Ashkenazi Jewish (ASJ) AF: 0.00643 AC: 95 AN: 14784

East Asian (EAS) AF: 0.0000379 AC: 1 AN: 26418

South Asian (SAS) AF: 0.00515 AC: 161 AN: 31246

European-Finnish (FIN) AF: 0.00468 AC: 111 AN: 23740

Middle Eastern (MID) AF: 0.00267 AC: 8 AN: 2998

European-Non Finnish (NFE) AF: 0.00865 AC: 8183 AN: 945930

Other (OTH) AF: 0.00792 AC: 356 AN: 44944

GnomAD4 genome AF: 0.00492 AC: 747 AN: 151712 Hom.: 1 Cov.: 32 AF XY: 0.00430 AC XY: 319 AN XY: 74140

African (AFR) AF: 0.00178 AC: 74 AN: 41482

American (AMR) AF: 0.00420 AC: 64 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00663 AC: 32 AN: 4828

European-Finnish (FIN) AF: 0.00230 AC: 24 AN: 10424

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00719 AC: 488 AN: 67826

Other (OTH) AF: 0.00569 AC: 12 AN: 2108

Alfa AF: 0.00466 Hom.: 0

Bravo AF: 0.00491

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	12
DANN	Uncertain	0.98
PhyloP100		0.47
PromoterAI		0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=100/0	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: rs527576288; hg19: chr1-17764915;