chr3-181712417-G-GGGC
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003106.4(SOX2):c.67_69dup(p.Gly23dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.00000314 in 1,594,764 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
SOX2
NM_003106.4 inframe_insertion
NM_003106.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.60
Genes affected
SOX2 (HGNC:11195): (SRY-box transcription factor 2) This intronless gene encodes a member of the SRY-related HMG-box (SOX) family of transcription factors involved in the regulation of embryonic development and in the determination of cell fate. The product of this gene is required for stem-cell maintenance in the central nervous system, and also regulates gene expression in the stomach. Mutations in this gene have been associated with optic nerve hypoplasia and with syndromic microphthalmia, a severe form of structural eye malformation. This gene lies within an intron of another gene called SOX2 overlapping transcript (SOX2OT). [provided by RefSeq, Jul 2008]
SOX2-OT (HGNC:20209): (SOX2 overlapping transcript) This gene produces alternatively spliced long non-coding RNAs. These RNAs were observed to be upregulated in tumor cells and positively correlated to expression of the SRY-box 2 gene. Overexpression of these transcripts may promote cell proliferation. [provided by RefSeq, Dec 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX2 | NM_003106.4 | c.67_69dup | p.Gly23dup | inframe_insertion | 1/1 | ENST00000325404.3 | |
SOX2-OT | NR_075091.1 | n.783-2758_783-2756dup | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX2 | ENST00000325404.3 | c.67_69dup | p.Gly23dup | inframe_insertion | 1/1 | NM_003106.4 | P1 | ||
SOX2-OT | ENST00000626948.3 | n.837-2758_837-2756dup | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000662 AC: 1AN: 151024Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000277 AC: 4AN: 1443740Hom.: 0 Cov.: 33 AF XY: 0.00000419 AC XY: 3AN XY: 716608
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Anophthalmia/microphthalmia-esophageal atresia syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | research | Anophthalmia/Microphthalmia Research Registry, Einstein Medical Center Philadelphia | - | Patient has symptoms similar to SOX2 related disease. However, similarly affected fetus did not have the same mutation - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at