chr19-35718030-G-A

Variant names:

• chr19-35718030-G-A
• rs1969020074
• NM_014727.3:c.12G>A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_014727.3(KMT2B):​c.12G>A​(p.Ala4Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000477 in 838,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: KMT2B NM_014727.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.390

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 Benign. Variant got -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 19-35718030-G-A is Benign according to our data. Variant chr19-35718030-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3239162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.39 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2B	NM_014727.3	c.12G>A	p.Ala4Ala	synonymous_variant	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.12G>A	p.Ala4Ala	synonymous_variant	Exon 1 of 37	1	NM_014727.3	ENSP00000398837.2
KMT2B	ENST00000673918.2	c.12G>A	p.Ala4Ala	synonymous_variant	Exon 1 of 37			ENSP00000501283.1
KMT2B	ENST00000687718.1	n.12G>A		non_coding_transcript_exon_variant	Exon 1 of 3			ENSP00000510535.1
KMT2B	ENST00000692961.1	n.12G>A		non_coding_transcript_exon_variant	Exon 1 of 36			ENSP00000509289.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000477 AC: 4 AN: 838114 Hom.: 0 Cov.: 31 AF XY: 0.00000516 AC XY: 2 AN XY: 387540

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: 0.00000261

Gnomad4 OTH exome AF: 0.0000362

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KMT2B: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Benign	0.88

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: rs1969020074; hg19: chr19-36208932;