2-112370196-A-G

Position:

• chr2-112370196-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001164463.1(RGPD8):​c.5280T>C​(p.Pro1760=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,551,778 control chromosomes in the GnomAD database, including 221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (3 hom., cov: 19)
  • Exomes 𝑓: 0.0021 (218 hom.)
• Consequence: RGPD8 NM_001164463.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.173

Genes affected

RGPD8 (HGNC:9849): (RANBP2 like and GRIP domain containing 8) 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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 2-112370196-A-G is Benign according to our data. Variant chr2-112370196-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2651275.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.173 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD8	NM_001164463.1	c.5280T>C	p.Pro1760=	synonymous_variant	23/23	ENST00000302558.8	NP_001157935.1
RGPD8	XM_024453101.2	c.5202T>C	p.Pro1734=	synonymous_variant	23/23		XP_024308869.1
RGPD8	XM_047445676.1	c.4425T>C	p.Pro1475=	synonymous_variant	18/18		XP_047301632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD8	ENST00000302558.8	c.5280T>C	p.Pro1760=	synonymous_variant	23/23	1	NM_001164463.1	ENSP00000306637	P1
RGPD8	ENST00000409750.5	c.4860T>C	p.Pro1620=	synonymous_variant	22/22	1		ENSP00000386511

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 216 AN: 140712 Hom.: 3 Cov.: 19

Gnomad AFR AF: 0.000393

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00242

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00171

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00200

Gnomad OTH AF: 0.00212

GnomAD3 exomes AF: 0.00235 AC: 567 AN: 241108 Hom.: 48 AF XY: 0.00271 AC XY: 352 AN XY: 129974

Gnomad AFR exome AF: 0.000627

Gnomad AMR exome AF: 0.000892

Gnomad ASJ exome AF: 0.00397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00671

Gnomad FIN exome AF: 0.000614

Gnomad NFE exome AF: 0.00247

Gnomad OTH exome AF: 0.00340

GnomAD4 exome AF: 0.00214 AC: 3025 AN: 1410986 Hom.: 218 Cov.: 30 AF XY: 0.00238 AC XY: 1670 AN XY: 701822

Gnomad4 AFR exome AF: 0.000279

Gnomad4 AMR exome AF: 0.000810

Gnomad4 ASJ exome AF: 0.00330

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00810

Gnomad4 FIN exome AF: 0.000418

Gnomad4 NFE exome AF: 0.00189

Gnomad4 OTH exome AF: 0.00262

GnomAD4 genome AF: 0.00153 AC: 215 AN: 140792 Hom.: 3 Cov.: 19 AF XY: 0.00155 AC XY: 106 AN XY: 68298

Gnomad4 AFR AF: 0.000392

Gnomad4 AMR AF: 0.00169

Gnomad4 ASJ AF: 0.00242

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00496

Gnomad4 FIN AF: 0.00171

Gnomad4 NFE AF: 0.00200

Gnomad4 OTH AF: 0.00210

Alfa AF: 0.00205 Hom.: 6

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

RGPD8: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.6
DANN	Benign	0.40

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: rs186330915; hg19: chr2-113127773;