chr14-39136338-T-C

Position:

• chr14-39136338-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GEMIN2	NM_003616.3	c.771-102T>C		intron_variant		ENST00000308317.12	NP_003607.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GEMIN2	ENST00000308317.12	c.771-102T>C		intron_variant		1	NM_003616.3	ENSP00000308533	P1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129364 AN: 151966 Hom.: 56120 Cov.: 31

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

Gnomad4 AFR exome AF: 0.670

Gnomad4 AMR exome AF: 0.836

Gnomad4 ASJ exome AF: 0.920

Gnomad4 EAS exome AF: 0.970

Gnomad4 SAS exome AF: 0.839

Gnomad4 FIN exome AF: 0.923

Gnomad4 NFE exome AF: 0.938

Gnomad4 OTH exome AF: 0.899

GnomAD4 genome AF: 0.851 AC: 129408 AN: 152084 Hom.: 56122 Cov.: 31 AF XY: 0.851 AC XY: 63236 AN XY: 74336

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.842

Gnomad4 ASJ AF: 0.919

Gnomad4 EAS AF: 0.952

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.931

Gnomad4 NFE AF: 0.935

Gnomad4 OTH AF: 0.869

Alfa AF: 0.916 Hom.: 29396

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
DANN	Benign	0.68

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

LitVar

Other links and lift over

dbSNP: rs9322993; hg19: chr14-39605542;