rs61462443

chr17-7846859-TACCACCACCACCACCACCACCACC-Tchr17-7846859-TACCACCACCACCACCACCACCACC-TACCchr17-7846859-TACCACCACCACCACCACCACCACC-TACCACCchr17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCchr17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCchr17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACCchr17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACCACCchr17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACCACCACCchr17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACCACCACCACCACCchr17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACCACCACCACCACCACCchr17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACCACCACCACCACCACCACCchr17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACCACCACCACCACCACCACCACCchr17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACCACCACCACCACCACCACCACCACCchr17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACCACCACCACCACCACCACCACCACCACCACCchr17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACCACCACCACCACCACCACCACCACCACCACCACC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001348716.2(KDM6B):c.768_791del(p.Pro257_Pro264del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000000911 in 1,097,542 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KDM6B NM_001348716.2 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67

Genes affected

KDM6B (HGNC:29012): (lysine demethylase 6B) The protein encoded by this gene is a lysine-specific demethylase that specifically demethylates di- or tri-methylated lysine 27 of histone H3 (H3K27me2 or H3K27me3). H3K27 trimethylation is a repressive epigenetic mark controlling chromatin organization and gene silencing. This protein can also demethylate non-histone proteins such as retinoblastoma protein. Through its demethylation actvity this gene influences cellular differentiation and development, tumorigenesis, inflammatory diseases, and neurodegenerative diseases. This protein has two classical nuclear localization signals at its N-terminus. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]

ACMG classification

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
KDM6B	NM_001348716.2	c.768_791del	p.Pro257_Pro264del	inframe_deletion	10/24	ENST00000448097.7
KDM6B	NM_001080424.2	c.768_791del	p.Pro257_Pro264del	inframe_deletion	9/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM6B	ENST00000448097.7	c.768_791del	p.Pro257_Pro264del	inframe_deletion	10/24	5	NM_001348716.2	A2
KDM6B	ENST00000254846.9	c.768_791del	p.Pro257_Pro264del	inframe_deletion	9/22	1		P2
KDM6B	ENST00000570632.1	c.711+135_711+158del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 118294 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097542 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 554650

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000123

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 118294 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 55440

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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: rs61462443; hg19: chr17-7750177;