chr19-35718020-TGGC-T

Variant names:

• chr19-35718020-TGGC-T
• rs898578503
• NM_014727.3:c.14_16delCGG

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_Supporting BS2

The NM_014727.3(KMT2B):​c.14_16delCGG​(p.Ala5del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 835,844 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: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KMT2B NM_014727.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

Genes affected

KMT2B (HGNC:15840): (lysine methyltransferase 2B) This gene encodes a protein which contains multiple domains including a CXXC zinc finger, three PHD zinc fingers, two FY-rich domains, and a SET (suppressor of variegation, enhancer of zeste, and trithorax) domain. The SET domain is a conserved C-terminal domain that characterizes proteins of the MLL (mixed-lineage leukemia) family. This gene is ubiquitously expressed in adult tissues. It is also amplified in solid tumor cell lines, and may be involved in human cancer. Two alternatively spliced transcript variants encoding distinct isoforms have been reported for this gene, however, the full length nature of the shorter transcript is not known. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_014727.3. Strenght limited to Supporting due to length of the change: 1aa.
• BS2: High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2B	NM_014727.3	c.14_16delCGG	p.Ala5del	disruptive_inframe_deletion	Exon 1 of 37	ENST00000420124.4	NP_055542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT2B	ENST00000420124.4	c.14_16delCGG	p.Ala5del	disruptive_inframe_deletion	Exon 1 of 37	1	NM_014727.3	ENSP00000398837.2
KMT2B	ENST00000673918.2	c.14_16delCGG	p.Ala5del	disruptive_inframe_deletion	Exon 1 of 37			ENSP00000501283.1
KMT2B	ENST00000687718.1	n.14_16delCGG		non_coding_transcript_exon_variant	Exon 1 of 3			ENSP00000510535.1
KMT2B	ENST00000692961.1	n.14_16delCGG		non_coding_transcript_exon_variant	Exon 1 of 36			ENSP00000509289.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 146450 Hom.: 0 Cov.: 32 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: 0.0000191 AC: 16 AN: 835844 Hom.: 0 AF XY: 0.0000233 AC XY: 9 AN XY: 386468

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000893

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.000265

Gnomad4 SAS exome AF: 0.000117

Gnomad4 FIN exome AF: 0.00146

Gnomad4 NFE exome AF: 0.0000131

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 146450 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71190

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

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs898578503; hg19: chr19-36208922;