chr17-43027847-C-T

Variant names:

• chr17-43027847-C-T
• rs915945
• NM_005440.5:c.301-214C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005440.5(RND2):​c.301-214C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,004 control chromosomes in the GnomAD database, including 7,186 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (7186 hom., cov: 32)
• Consequence: RND2 NM_005440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• Publications: 18 publications found

Genes affected

RND2 (HGNC:18315): (Rho family GTPase 2) This gene encodes a member of the Rho GTPase family, whose members play a key role in the regulation of actin cytoskeleton organization in response to extracellular growth factors. This particular family member has been implicated in the regulation of neuronal morphology and endosomal trafficking. The gene localizes to chromosome 17 and is the centromeric neighbor of the breast-ovarian cancer susceptibility gene BRCA1. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005440.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RND2	NM_005440.5	MANE Select	c.301-214C>T		intron	N/A	NP_005431.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RND2	ENST00000587250.4	TSL:1 MANE Select	c.301-214C>T		intron	N/A	ENSP00000466680.1
	RND2	ENST00000710494.1		n.229-214C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44739 AN: 151886 Hom.: 7187 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.315

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.294 AC: 44733 AN: 152004 Hom.: 7186 Cov.: 32 AF XY: 0.300 AC XY: 22288 AN XY: 74258

African (AFR) AF: 0.179 AC: 7420 AN: 41472

American (AMR) AF: 0.263 AC: 4024 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1218 AN: 3468

East Asian (EAS) AF: 0.369 AC: 1903 AN: 5158

South Asian (SAS) AF: 0.493 AC: 2372 AN: 4812

European-Finnish (FIN) AF: 0.404 AC: 4258 AN: 10546

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22503 AN: 67948

Other (OTH) AF: 0.320 AC: 675 AN: 2110

Alfa AF: 0.304 Hom.: 9358

Bravo AF: 0.273

Asia WGS AF: 0.400 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.5
DANN	Benign	0.57
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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: rs915945; hg19: chr17-41179864;