12-49039502-C-G

Variant names:

• chr12-49039502-C-G
• NM_003482.4:c.8162G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003482.4(KMT2D):​c.8162G>C​(p.Gly2721Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KMT2D NM_003482.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

Genes affected

KMT2D (HGNC:7133): (lysine methyltransferase 2D) The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1563217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2D	NM_003482.4	c.8162G>C	p.Gly2721Ala	missense_variant	Exon 33 of 55	ENST00000301067.12	NP_003473.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT2D	ENST00000301067.12	c.8162G>C	p.Gly2721Ala	missense_variant	Exon 33 of 55	5	NM_003482.4	ENSP00000301067.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.89	N
REVEL	Uncertain	0.33
Sift	Benign	0.031	D
Polyphen		0.30	B
Vest4		0.15
MutPred		0.20		Loss of catalytic residue at P2717 (P = 0.1146);
MVP		0.31
MPC		0.19
ClinPred		0.30	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.044
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-49433285;