2-87866942-T-C

Variant names:

• chr2-87866942-T-C
• rs9636470
• XM_017004845.2:c.307-48319A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The XM_017004845.2(RGPD2):​c.307-48319A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 100,014 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.

• Frequency: Genomes: 𝑓 0.13 (0 hom., cov: 30)
• Consequence: RGPD2 XM_017004845.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• Publications: 5 publications found

Genes affected

RGPD2 (HGNC:32415): (RANBP2 like and GRIP domain containing 2) Predicted to contribute to GTPase activator activity. Predicted to be involved in NLS-bearing protein import into nucleus. Predicted to be part of nuclear pore. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Variant has high frequency in the EAS (0.202) population. However there is too low homozygotes in high coverage region: (expected more than 454, got 0).
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD2	XM_017004845.2	c.307-48319A>G		intron_variant	Intron 4 of 25		XP_016860334.2
RGPD2	XM_047445734.1	c.232-48319A>G		intron_variant	Intron 3 of 24		XP_047301690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.135 AC: 13477 AN: 99894 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.135 AC: 13484 AN: 100014 Hom.: 0 Cov.: 30 AF XY: 0.0710 AC XY: 3440 AN XY: 48436

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0380 AC: 1254 AN: 33010

American (AMR) AF: 0.155 AC: 1437 AN: 9296

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 457 AN: 2012

East Asian (EAS) AF: 0.216 AC: 631 AN: 2918

South Asian (SAS) AF: 0.136 AC: 402 AN: 2962

European-Finnish (FIN) AF: 0.108 AC: 703 AN: 6492

Middle Eastern (MID) AF: 0.0990 AC: 20 AN: 202

European-Non Finnish (NFE) AF: 0.202 AC: 8318 AN: 41206

Other (OTH) AF: 0.144 AC: 195 AN: 1350

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0779 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9636470; hg19: chr2-88166461;