rs7781309

Variant names:

• chr7-152354105-T-C
• rs7781309
• NM_170606.3:c.250+4482A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170606.3(KMT2C):​c.250+4482A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,046 control chromosomes in the GnomAD database, including 12,448 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (12448 hom., cov: 32)
• Consequence: KMT2C NM_170606.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.14
• Publications: 6 publications found

Genes affected

KMT2C (HGNC:13726): (lysine methyltransferase 2C) This gene is a member of the myeloid/lymphoid or mixed-lineage leukemia (MLL) family and encodes a nuclear protein with an AT hook DNA-binding domain, a DHHC-type zinc finger, six PHD-type zinc fingers, a SET domain, a post-SET domain and a RING-type zinc finger. This protein is a member of the ASC-2/NCOA6 complex (ASCOM), which possesses histone methylation activity and is involved in transcriptional coactivation. [provided by RefSeq, Jul 2008]

KMT2C Gene-Disease associations (from GenCC):

• Kleefstra syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Illumina, Ambry Genetics, Broad Center for Mendelian Genomics
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170606.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KMT2C	NM_170606.3	MANE Select	c.250+4482A>G		intron	N/A	NP_733751.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KMT2C	ENST00000262189.11	TSL:1 MANE Select	c.250+4482A>G		intron	N/A	ENSP00000262189.6
	KMT2C	ENST00000682283.1		c.250+4482A>G		intron	N/A	ENSP00000507485.1
	KMT2C	ENST00000679882.1		c.250+4482A>G		intron	N/A	ENSP00000506154.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50418 AN: 151928 Hom.: 12412 Cov.: 32

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.332 AC: 50509 AN: 152046 Hom.: 12448 Cov.: 32 AF XY: 0.335 AC XY: 24881 AN XY: 74322

African (AFR) AF: 0.697 AC: 28892 AN: 41440

American (AMR) AF: 0.232 AC: 3545 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 880 AN: 3468

East Asian (EAS) AF: 0.314 AC: 1621 AN: 5160

South Asian (SAS) AF: 0.285 AC: 1372 AN: 4822

European-Finnish (FIN) AF: 0.276 AC: 2918 AN: 10562

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10532 AN: 67998

Other (OTH) AF: 0.295 AC: 622 AN: 2106

Alfa AF: 0.214 Hom.: 15976

Bravo AF: 0.344

Asia WGS AF: 0.335 AC: 1162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.40
DANN	Benign	0.24
PhyloP100		-4.1
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: rs7781309; hg19: chr7-152051190;