1-17438419-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_018715.4(RCC2):​c.96G>T​(p.Ala32Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000267 in 1,121,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A32A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RCC2 NM_018715.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=0.467 with no splicing effect.

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000267 AC: 3 AN: 1121554 Hom.: 0 Cov.: 30 AF XY: 0.00000186 AC XY: 1 AN XY: 538670

African (AFR) AF: 0.00 AC: 0 AN: 22890

American (AMR) AF: 0.00 AC: 0 AN: 8602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14784

East Asian (EAS) AF: 0.00 AC: 0 AN: 26418

South Asian (SAS) AF: 0.00 AC: 0 AN: 31246

European-Finnish (FIN) AF: 0.000126 AC: 3 AN: 23740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2998

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 945932

Other (OTH) AF: 0.00 AC: 0 AN: 44944

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	11
DANN	Benign	0.94
PhyloP100		0.47
PromoterAI		0.032	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;