NM_001197104.2:c.11071+236C>T

Variant names:

• chr11-118510354-C-T
• rs9332852
• NM_001197104.2:c.11071+236C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001197104.2(KMT2A):​c.11071+236C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 152,252 control chromosomes in the GnomAD database, including 191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.043 (191 hom., cov: 32)
• Consequence: KMT2A NM_001197104.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.413
• Publications: 5 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=-0.89).
• BP6: Variant 11-118510354-C-T is Benign according to our data. Variant chr11-118510354-C-T is described in ClinVar as [Benign]. Clinvar id is 1269309.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2A	NM_001197104.2	c.11071+236C>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.11071+236C>T		intron_variant	Intron 30 of 35	1	NM_001197104.2	ENSP00000436786.2

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6482 AN: 152134 Hom.: 191 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.0740

Gnomad FIN AF: 0.0818

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0587

Gnomad OTH AF: 0.0354

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

GnomAD4 genome AF: 0.0426 AC: 6481 AN: 152252 Hom.: 191 Cov.: 32 AF XY: 0.0435 AC XY: 3240 AN XY: 74448

African (AFR) AF: 0.0122 AC: 506 AN: 41562

American (AMR) AF: 0.0255 AC: 390 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 177 AN: 3470

East Asian (EAS) AF: 0.0208 AC: 108 AN: 5184

South Asian (SAS) AF: 0.0745 AC: 359 AN: 4818

European-Finnish (FIN) AF: 0.0818 AC: 867 AN: 10594

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0587 AC: 3990 AN: 68002

Other (OTH) AF: 0.0350 AC: 74 AN: 2112

Alfa AF: 0.0494 Hom.: 33

Bravo AF: 0.0372

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 10, 2018

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	-0.89
CADD	Benign	2.5
DANN	Benign	0.61
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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: rs9332852; hg19: chr11-118381069; COSMIC: COSV104417805;