chr2-112388078-A-C

Position:

• chr2-112388078-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000302558.8(RGPD8):​c.4867T>G​(p.Ser1623Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.0000030 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD8 ENST00000302558.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.122

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03732723).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD8	NM_001164463.1	c.4867T>G	p.Ser1623Ala	missense_variant	20/23	ENST00000302558.8	NP_001157935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD8	ENST00000302558.8	c.4867T>G	p.Ser1623Ala	missense_variant	20/23	1	NM_001164463.1	ENSP00000306637.3
RGPD8	ENST00000409750.5	c.4447T>G	p.Ser1483Ala	missense_variant	19/22	1		ENSP00000386511.1

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000301 AC: 3 AN: 995502 Hom.: 0 Cov.: 14 AF XY: 0.00000600 AC XY: 3 AN XY: 499780

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000547

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000225

GnomAD4 genome Cov.: 16

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

The c.4867T>G (p.S1623A) alteration is located in exon 20 (coding exon 20) of the RGPD8 gene. This alteration results from a T to G substitution at nucleotide position 4867, causing the serine (S) at amino acid position 1623 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.3
DANN	Benign	0.46
DEOGEN2	Benign	0.0014	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.60	N;N
REVEL	Benign	0.017
Sift	Benign	0.30	T;T
Sift4G	Benign	0.69	T;T
Polyphen		0.0050	B;.
Vest4		0.069
MutPred		0.35		Gain of helix (P = 6e-04);.;
MVP		0.014
ClinPred		0.045	T
GERP RS		-4.5
Varity_R		0.11
gMVP		0.020

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-113145655;