chr19-35718099-CGGCGGGGGCGGG-C

Variant names:

• chr19-35718099-CGGCGGGGGCGGG-C
• rs1275530480
• NM_014727.3:c.85_96delGGGGGCGGGGGC

Variant summary

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

The NM_014727.3(KMT2B):​c.85_96delGGGGGCGGGGGC​(p.Gly29_Gly32del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 146,576 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 0.0000068 (0 hom., cov: 32)
• Consequence: KMT2B NM_014727.3 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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 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_014727.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2B	NM_014727.3	c.85_96delGGGGGCGGGGGC	p.Gly29_Gly32del	conservative_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.85_96delGGGGGCGGGGGC	p.Gly29_Gly32del	conservative_inframe_deletion	Exon 1 of 37	1	NM_014727.3	ENSP00000398837.2
KMT2B	ENST00000673918.2	c.85_96delGGGGGCGGGGGC	p.Gly29_Gly32del	conservative_inframe_deletion	Exon 1 of 37			ENSP00000501283.1
KMT2B	ENST00000687718.1	n.85_96delGGGGGCGGGGGC		non_coding_transcript_exon_variant	Exon 1 of 3			ENSP00000510535.1
KMT2B	ENST00000692961.1	n.85_96delGGGGGCGGGGGC		non_coding_transcript_exon_variant	Exon 1 of 36			ENSP00000509289.1

Frequencies

GnomAD3 genomes AF: 0.00000682 AC: 1 AN: 146576 Hom.: 0 Cov.: 32

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: 0.0000152

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000682 AC: 1 AN: 146576 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71304

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: 0.0000152

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

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: rs1275530480; hg19: chr19-36209001;