NM_001197104.2:c.11430-142A>G

Variant names:

• chr11-118520660-A-G
• rs576950
• NM_001197104.2:c.11430-142A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001197104.2(KMT2A):​c.11430-142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 602,186 control chromosomes in the GnomAD database, including 41,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9220 hom., cov: 29)
  • Exomes 𝑓: 0.37 (32384 hom.)
• Consequence: KMT2A NM_001197104.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25
• Publications: 10 publications found

Genes affected

KMT2A (HGNC:7132): (lysine methyltransferase 2A) This gene encodes a transcriptional coactivator that plays an essential role in regulating gene expression during early development and hematopoiesis. The encoded protein contains multiple conserved functional domains. One of these domains, the SET domain, is responsible for its histone H3 lysine 4 (H3K4) methyltransferase activity which mediates chromatin modifications associated with epigenetic transcriptional activation. This protein is processed by the enzyme Taspase 1 into two fragments, MLL-C and MLL-N. These fragments reassociate and further assemble into different multiprotein complexes that regulate the transcription of specific target genes, including many of the HOX genes. Multiple chromosomal translocations involving this gene are the cause of certain acute lymphoid leukemias and acute myeloid leukemias. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]

TTC36-AS1 (HGNC:55495): (TTC36 and KMT2A antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-118520660-A-G is Benign according to our data. Variant chr11-118520660-A-G is described in ClinVar as Benign. ClinVar VariationId is 1242710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001197104.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KMT2A	NM_001197104.2	MANE Select	c.11430-142A>G		intron	N/A	NP_001184033.1
	KMT2A	NM_001412597.1		c.11520-142A>G		intron	N/A	NP_001399526.1
	KMT2A	NM_005933.4		c.11421-142A>G		intron	N/A	NP_005924.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KMT2A	ENST00000534358.8	TSL:1 MANE Select	c.11430-142A>G		intron	N/A	ENSP00000436786.2
	KMT2A	ENST00000389506.10	TSL:1	c.11421-142A>G		intron	N/A	ENSP00000374157.5
	KMT2A	ENST00000531904.7	TSL:2	c.11529-142A>G		intron	N/A	ENSP00000432391.3

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47766 AN: 151434 Hom.: 9225 Cov.: 29

Gnomad AFR AF: 0.0922

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.368 AC: 166045 AN: 450634 Hom.: 32384 Cov.: 5 AF XY: 0.363 AC XY: 85830 AN XY: 236756

African (AFR) AF: 0.0892 AC: 1094 AN: 12264

American (AMR) AF: 0.313 AC: 5921 AN: 18926

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 5823 AN: 13238

East Asian (EAS) AF: 0.154 AC: 4642 AN: 30208

South Asian (SAS) AF: 0.216 AC: 9112 AN: 42130

European-Finnish (FIN) AF: 0.392 AC: 16383 AN: 41792

Middle Eastern (MID) AF: 0.373 AC: 711 AN: 1908

European-Non Finnish (NFE) AF: 0.427 AC: 113145 AN: 265280

Other (OTH) AF: 0.370 AC: 9214 AN: 24888

GnomAD4 genome AF: 0.315 AC: 47750 AN: 151552 Hom.: 9220 Cov.: 29 AF XY: 0.311 AC XY: 23034 AN XY: 74022

African (AFR) AF: 0.0919 AC: 3804 AN: 41390

American (AMR) AF: 0.353 AC: 5365 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1565 AN: 3462

East Asian (EAS) AF: 0.186 AC: 956 AN: 5150

South Asian (SAS) AF: 0.211 AC: 1012 AN: 4794

European-Finnish (FIN) AF: 0.380 AC: 3957 AN: 10422

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29918 AN: 67822

Other (OTH) AF: 0.357 AC: 746 AN: 2092

Alfa AF: 0.367 Hom.: 21093

Bravo AF: 0.304

Asia WGS AF: 0.192 AC: 667 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.32
DANN	Benign	0.15
PhyloP100		-1.2
Mutation Taster		=26/74	disease causing (long InDel)

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

Other links and lift over

dbSNP: rs576950; hg19: chr11-118391375;