X-44873590-T-TGCCGCC
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2
The NM_001291415.2(KDM6A):c.45_50dupCGCCGC(p.Ala16_Ala17dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000133 in 1,203,950 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.000010 ( 0 hom. 0 hem. )
Consequence
KDM6A
NM_001291415.2 disruptive_inframe_insertion
NM_001291415.2 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.02
Genes affected
KDM6A (HGNC:12637): (lysine demethylase 6A) This gene is located on the X chromosome and is the corresponding locus to a Y-linked gene which encodes a tetratricopeptide repeat (TPR) protein. The encoded protein of this gene contains a JmjC-domain and catalyzes the demethylation of tri/dimethylated histone H3. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_001291415.2
BP6
Variant X-44873590-T-TGCCGCC is Benign according to our data. Variant chrX-44873590-T-TGCCGCC is described in ClinVar as [Likely_benign]. Clinvar id is 1212225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000101 (11/1093231) while in subpopulation AFR AF= 0.00038 (10/26347). AF 95% confidence interval is 0.000206. There are 0 homozygotes in gnomad4_exome. There are 0 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KDM6A | NM_001291415.2 | c.45_50dupCGCCGC | p.Ala16_Ala17dup | disruptive_inframe_insertion | 1/30 | ENST00000611820.5 | NP_001278344.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KDM6A | ENST00000611820.5 | c.45_50dupCGCCGC | p.Ala16_Ala17dup | disruptive_inframe_insertion | 1/30 | 1 | NM_001291415.2 | ENSP00000483595.2 |
Frequencies
GnomAD3 genomes AF: 0.0000452 AC: 5AN: 110719Hom.: 0 Cov.: 23 AF XY: 0.0000600 AC XY: 2AN XY: 33353
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GnomAD3 exomes AF: 0.0000242 AC: 4AN: 165211Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 58141
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GnomAD4 exome AF: 0.0000101 AC: 11AN: 1093231Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 360199
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GnomAD4 genome AF: 0.0000452 AC: 5AN: 110719Hom.: 0 Cov.: 23 AF XY: 0.0000600 AC XY: 2AN XY: 33353
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Kabuki syndrome 2 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 14, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 30, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 21, 2022 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at