17-43027847-C-T

Position:

• chr17-43027847-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RND2	NM_005440.5	c.301-214C>T		intron_variant		ENST00000587250.4
RND2	XM_011525316.2	c.301-214C>T		intron_variant
RND2	XM_011525317.3	c.217-214C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RND2	ENST00000587250.4	c.301-214C>T		intron_variant		1	NM_005440.5	P1
RND2	ENST00000710494.1	n.229-214C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.320

Alfa AF: 0.307 Hom.: 7357

Bravo AF: 0.273

Asia WGS AF: 0.400 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.5
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs915945; hg19: chr17-41179864;