chr12-49019797-TA-T

Position:

• chr12-49019797-TA-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003482.4(KMT2D):​c.*1982delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 189,624 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00094 (0 hom., cov: 31)
  • Exomes 𝑓: 0.079 (0 hom.)
• Consequence: KMT2D NM_003482.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.157

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]

ENSG00000288710 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KMT2D	NM_003482.4	c.*1982delT		3_prime_UTR_variant	55/55	ENST00000301067.12	NP_003473.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KMT2D	ENST00000301067	c.*1982delT		3_prime_UTR_variant	55/55	5	NM_003482.4	ENSP00000301067.7
ENSG00000288710	ENST00000683988.1	n.*76+1906delT		intron_variant				ENSP00000506939.1

Frequencies

GnomAD3 genomes AF: 0.000917 AC: 134 AN: 146098 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000395

Gnomad SAS AF: 0.00216

Gnomad FIN AF: 0.00307

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000394

Gnomad OTH AF: 0.000506

GnomAD4 exome AF: 0.0795 AC: 3453 AN: 43460 Hom.: 0 Cov.: 0 AF XY: 0.0792 AC XY: 1594 AN XY: 20136

Gnomad4 AFR exome AF: 0.0708

Gnomad4 AMR exome AF: 0.0705

Gnomad4 ASJ exome AF: 0.0842

Gnomad4 EAS exome AF: 0.0803

Gnomad4 SAS exome AF: 0.0742

Gnomad4 FIN exome AF: 0.0187

Gnomad4 NFE exome AF: 0.0804

Gnomad4 OTH exome AF: 0.0825

GnomAD4 genome AF: 0.000937 AC: 137 AN: 146164 Hom.: 0 Cov.: 31 AF XY: 0.00106 AC XY: 75 AN XY: 71052

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.00156

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000396

Gnomad4 SAS AF: 0.00216

Gnomad4 FIN AF: 0.00307

Gnomad4 NFE AF: 0.000409

Gnomad4 OTH AF: 0.000503

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Kabuki syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs879897260; hg19: chr12-49413580;