X-123614070-GTCCTTT-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001081550.2(THOC2):c.4425_4430del(p.Glu1475_Lys1476del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000275 in 1,091,619 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
• Consequence: THOC2 NM_001081550.2 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.84

Genes affected

THOC2 (HGNC:19073): (THO complex subunit 2) The TREX multiprotein complex binds specifically to spliced mRNAs to facilitate mRNA export. The protein encoded by this gene is a member of the THO complex, a subset of the TREX complex. The encoded protein interacts with the THOC1 protein.[provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001081550.2.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THOC2	NM_001081550.2	c.4425_4430del	p.Glu1475_Lys1476del	inframe_deletion	34/39	ENST00000245838.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THOC2	ENST00000245838.13	c.4425_4430del	p.Glu1475_Lys1476del	inframe_deletion	34/39	5	NM_001081550.2	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000275 AC: 3 AN: 1091619 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 359101

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000996

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.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 2 amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs759270626; hg19: chrX-122747921;