Genetic Variant GEMIN2:c.771-102T>C (chr14-39136338-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003616.3(GEMIN2):c.771-102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 681,914 control chromosomes in the GnomAD database, including 278,045 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.85 ( 56122 hom., cov: 31)

Exomes 𝑓: 0.91 ( 221923 hom. )

Consequence

GEMIN2
NM_003616.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.494

Publications

5 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN2	NM_003616.3 link	c.771-102T>C		intron_variant	Intron 9 of 9	ENST00000308317.12	NP_003607.2	O14893-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GEMIN2	ENST00000308317.12 link	c.771-102T>C		intron_variant	Intron 9 of 9	1	NM_003616.3	ENSP00000308533.7		O14893-5

Frequencies

GnomAD3 genomes

AF:

0.851

AC:

129364

AN:

151966

Hom.:

56120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.674

Gnomad AMI

AF:

0.968

Gnomad AMR

AF:

0.842

Gnomad ASJ

AF:

0.919

Gnomad EAS

AF:

0.952

Gnomad SAS

AF:

0.845

Gnomad FIN

AF:

0.931

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.935

Gnomad OTH

AF:

0.874

GnomAD4 exome

AF:

0.913

AC:

483921

AN:

529830

Hom.:

221923

AF XY:

0.912

AC XY:

262295

AN XY:

287728

show subpopulations

African (AFR)

AF:

0.670

AC:

9067

AN:

13542

American (AMR)

AF:

0.836

AC:

21918

AN:

26206

Ashkenazi Jewish (ASJ)

AF:

0.920

AC:

16443

AN:

17880

East Asian (EAS)

AF:

0.970

AC:

30818

AN:

31780

South Asian (SAS)

AF:

0.839

AC:

45266

AN:

53942

European-Finnish (FIN)

AF:

0.923

AC:

39814

AN:

43146

Middle Eastern (MID)

AF:

0.880

AC:

3275

AN:

3722

European-Non Finnish (NFE)

AF:

0.938

AC:

291318

AN:

310702

Other (OTH)

AF:

0.899

AC:

26002

AN:

28910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1848

3695

5543

7390

9238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1136

2272

3408

4544

5680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.851

AC:

129408

AN:

152084

Hom.:

56122

Cov.:

AF XY:

0.851

AC XY:

63236

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.673

AC:

27888

AN:

41410

American (AMR)

AF:

0.842

AC:

12856

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.919

AC:

3188

AN:

3470

East Asian (EAS)

AF:

0.952

AC:

4933

AN:

5180

South Asian (SAS)

AF:

0.845

AC:

4075

AN:

4820

European-Finnish (FIN)

AF:

0.931

AC:

9866

AN:

10598

Middle Eastern (MID)

AF:

0.864

AC:

254

AN:

294

European-Non Finnish (NFE)

AF:

0.935

AC:

63631

AN:

68022

Other (OTH)

AF:

0.869

AC:

1836

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

844

1688

2531

3375

4219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

884

1768

2652

3536

4420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.914

Hom.:

32864

Bravo

AF:

0.838

Asia WGS

AF:

0.859

AC:

2988

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.3

(source)

DANN

Benign

0.68

PhyloP100

-0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over