2-86987031-C-G

Position:

• chr2-86987031-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001382344.1(RGPD1):​c.4132C>G​(p.Gln1378Glu) variant causes a missense change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 17)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD1 NM_001382344.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD1	NM_001382344.1	c.4132C>G	p.Gln1378Glu	missense_variant	20/23	ENST00000641458.2	NP_001369273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD1	ENST00000641458.2	c.4132C>G	p.Gln1378Glu	missense_variant	20/23		NM_001382344.1	ENSP00000492954.1
RGPD1	ENST00000398193.8	c.4132C>G	p.Gln1378Glu	missense_variant	20/23	1		ENSP00000381253.3
RGPD1	ENST00000428128.1	n.*2051C>G		non_coding_transcript_exon_variant	7/10	1		ENSP00000402729.1
RGPD1	ENST00000428128.1	n.*2051C>G		3_prime_UTR_variant	7/10	1		ENSP00000402729.1

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.95e-7 AC: 1 AN: 1438994 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 717274

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000225

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.: 17

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

Nov 26, 2024

The c.4108C>G (p.Q1370E) alteration is located in exon 20 (coding exon 20) of the RGPD1 gene. This alteration results from a C to G substitution at nucleotide position 4108, causing the glutamine (Q) at amino acid position 1370 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	Uncertain	0.43
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.065	T;.;T;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.097
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D;D;.;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.4	L;.;L;.
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-2.0	N;N;N;.
REVEL	Benign	0.20
Sift	Benign	0.092	T;T;T;.
Sift4G	Benign	0.18	T;T;T;.
Polyphen		0.92	.;P;.;.
Vest4		0.52
MutPred		0.60		.;Loss of MoRF binding (P = 0.0298);.;Loss of MoRF binding (P = 0.0298);
MVP		0.13
ClinPred		0.58	D
GERP RS		2.4
Varity_R		0.28
gMVP		0.011

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: chr2-87214154;