2-86951349-T-A

Position:

• chr2-86951349-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001382344.1(RGPD1):​c.126T>A​(p.Asp42Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 6)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD1 NM_001382344.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.519

Genes affected

RGPD1 (HGNC:32414): (RANBP2 like and GRIP domain containing 1) 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07075617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD1	NM_001382344.1	c.126T>A	p.Asp42Glu	missense_variant	2/23	ENST00000641458.2	NP_001369273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD1	ENST00000641458.2	c.126T>A	p.Asp42Glu	missense_variant	2/23		NM_001382344.1	ENSP00000492954.1
RGPD1	ENST00000398193.8	c.126T>A	p.Asp42Glu	missense_variant	2/23	1		ENSP00000381253.3
RGPD1	ENST00000641339.1	n.*269T>A		non_coding_transcript_exon_variant	4/5			ENSP00000492933.1
RGPD1	ENST00000641339.1	n.*269T>A		3_prime_UTR_variant	4/5			ENSP00000492933.1

Frequencies

GnomAD3 genomes Cov.: 6

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000207 AC: 1 AN: 482926 Hom.: 0 Cov.: 6 AF XY: 0.00000407 AC XY: 1 AN XY: 245538

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000627

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 6

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

Oct 03, 2023

The c.102T>A (p.D34E) alteration is located in exon 2 (coding exon 2) of the RGPD1 gene. This alteration results from a T to A substitution at nucleotide position 102, causing the aspartic acid (D) at amino acid position 34 to be replaced by a glutamic acid (E). 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	0.15
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.85
DEOGEN2	Benign	0.021	T;.;T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.84	T;T;.;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.071	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.13	N;.;N;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.1	N;N;N;.
REVEL	Benign	0.029
Sift	Benign	0.51	T;T;T;.
Sift4G	Benign	1.0	T;T;T;.
Polyphen		0.014	.;B;.;.
Vest4		0.23
MutPred		0.24		.;Gain of ubiquitination at K46 (P = 0.0522);.;Gain of ubiquitination at K46 (P = 0.0522);
MVP		0.048
ClinPred		0.10	T
GERP RS		2.4
Varity_R		0.070
gMVP		0.014

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1680553215; hg19: chr2-87178472;