2-38754065-G-A

Position:

• chr2-38754065-G-A

Variant summary

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

The ENST00000409011.5(GEMIN6):​c.-281+2247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,052 control chromosomes in the GnomAD database, including 24,874 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 0.55 (24874 hom., cov: 33)
• Consequence: GEMIN6 ENST00000409011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276

Genes affected

GEMIN6 (HGNC:20044): (gem nuclear organelle associated protein 6) GEMIN6 is part of a large macromolecular complex, localized to both the cytoplasm and the nucleus, that plays a role in the cytoplasmic assembly of small nuclear ribonucleoproteins (snRNPs). Other members of this complex include SMN (MIM 600354), GEMIN2 (SIP1; MIM 602595), GEMIN3 (DDX20; MIM 606168), GEMIN4 (MIM 606969), and GEMIN5 (MIM 607005).[supplied by OMIM, Jul 2002]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GEMIN6	ENST00000409011.5	c.-281+2247G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83974 AN: 151934 Hom.: 24868 Cov.: 33

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.595

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.552 AC: 84004 AN: 152052 Hom.: 24874 Cov.: 33 AF XY: 0.560 AC XY: 41593 AN XY: 74330

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.598

Alfa AF: 0.561 Hom.: 3624

Bravo AF: 0.539

Asia WGS AF: 0.765 AC: 2658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10197412; hg19: chr2-38981207;