Variant 14-39128295-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003616.3(GEMIN2):c.547G>A(p.Val183Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000899 in 1,557,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000092 ( 0 hom. )

Consequence

GEMIN2
NM_003616.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.22

Variant links:

Genes affected

GEMIN2 (HGNC:10884): (gem nuclear organelle associated protein 2) This gene encodes one of the proteins found in the SMN complex, which consists of several gemin proteins and the protein known as the survival of motor neuron protein. The SMN complex is localized to a subnuclear compartment called gems (gemini of coiled bodies) and is required for assembly of spliceosomal snRNPs and for pre-mRNA splicing. This protein interacts directly with the survival of motor neuron protein and it is required for formation of the SMN complex. A knockout mouse targeting the mouse homolog of this gene exhibited disrupted snRNP assembly and motor neuron degeneration. [provided by RefSeq, Aug 2011]

GEMIN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36468554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GEMIN2	NM_003616.3 link	c.547G>A	p.Val183Ile	missense_variant	7/10	ENST00000308317.12	NP_003607.2	O14893-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GEMIN2	ENST00000308317.12 link	c.547G>A	p.Val183Ile	missense_variant	7/10	1	NM_003616.3	ENSP00000308533.7		O14893-5

Frequencies

GnomAD3 genomes

AF:

0.00000665

AC:

AN:

150350

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242974

Hom.:

AF XY:

0.00000760

AC XY:

AN XY:

131558

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000924

AC:

AN:

1406930

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

702832

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000232

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000204

Gnomad4 NFE exome

AF:

0.0000103

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000665

AC:

AN:

150350

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2023

The c.580G>A (p.V194I) alteration is located in exon 7 (coding exon 7) of the GEMIN2 gene. This alteration results from a G to A substitution at nucleotide position 580, causing the valine (V) at amino acid position 194 to be replaced by an isoleucine (I). 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

0.17

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.078

T;.;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.0038

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.5

M;M;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.19

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.25

T;T;T

Sift4G

Uncertain

0.057

T;T;T

Polyphen

0.0040

B;B;B

Vest4

0.58

MutPred

0.55

Gain of catalytic residue at V191 (P = 8e-04);Gain of catalytic residue at V191 (P = 8e-04);.;

MVP

0.70

MPC

0.14

ClinPred

0.59

GERP RS

5.8

Varity_R

0.17

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over