rs112584352

Variant names:

• chr11-118511907-C-T
• rs112584352
• NM_001197104.2:c.11072-44C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001197104.2(KMT2A):​c.11072-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 1,471,732 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (2 hom.)
• Consequence: KMT2A NM_001197104.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.943
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-118511907-C-T is Benign according to our data. Variant chr11-118511907-C-T is described in ClinVar as [Benign]. Clinvar id is 1260051.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0013 (198/152334) while in subpopulation AFR AF = 0.00428 (178/41572). AF 95% confidence interval is 0.00377. There are 0 homozygotes in GnomAd4. There are 96 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 198 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2A	NM_001197104.2	c.11072-44C>T		intron_variant	Intron 30 of 35	ENST00000534358.8	NP_001184033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT2A	ENST00000534358.8	c.11072-44C>T		intron_variant	Intron 30 of 35	1	NM_001197104.2	ENSP00000436786.2

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 193 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000517 AC: 128 AN: 247694 AF XY: 0.000396

Gnomad AFR exome AF: 0.00456

Gnomad AMR exome AF: 0.000234

Gnomad ASJ exome AF: 0.00402

Gnomad EAS exome AF: 0.0000551

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000269

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.000279 AC: 368 AN: 1319398 Hom.: 2 Cov.: 20 AF XY: 0.000240 AC XY: 159 AN XY: 663680

African (AFR) AF: 0.00527 AC: 162 AN: 30750

American (AMR) AF: 0.000226 AC: 10 AN: 44332

Ashkenazi Jewish (ASJ) AF: 0.00408 AC: 103 AN: 25236

East Asian (EAS) AF: 0.0000768 AC: 3 AN: 39048

South Asian (SAS) AF: 0.0000362 AC: 3 AN: 82898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.00109 AC: 6 AN: 5488

European-Non Finnish (NFE) AF: 0.0000193 AC: 19 AN: 982596

Other (OTH) AF: 0.00111 AC: 62 AN: 55814

GnomAD4 genome AF: 0.00130 AC: 198 AN: 152334 Hom.: 0 Cov.: 32 AF XY: 0.00129 AC XY: 96 AN XY: 74482

African (AFR) AF: 0.00428 AC: 178 AN: 41572

American (AMR) AF: 0.000327 AC: 5 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68034

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00128 Hom.: 0

Bravo AF: 0.00165

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 23, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.69
PhyloP100		-0.94

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: rs112584352; hg19: chr11-118382622;