12-49019797-TAAA-TAAAA

Variant names:

• chr12-49019797-T-TA
• rs879897260
• NM_003482.4:c.*1982dupT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_003482.4(KMT2D):​c.*1982dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00552 in 195,534 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 31)
  • Exomes 𝑓: 0.020 (0 hom.)
• Consequence: KMT2D NM_003482.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000649 (95/146368) while in subpopulation SAS AF= 0.00108 (5/4630). AF 95% confidence interval is 0.000732. There are 0 homozygotes in gnomad4. There are 39 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 95 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2D	NM_003482.4	c.*1982dupT		3_prime_UTR_variant	Exon 55 of 55	ENST00000301067.12	NP_003473.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT2D	ENST00000301067	c.*1982dupT		3_prime_UTR_variant	Exon 55 of 55	5	NM_003482.4	ENSP00000301067.7
ENSG00000288710	ENST00000683988.1	n.*76+1906dupT		intron_variant	Intron 5 of 15			ENSP00000506939.1

Frequencies

GnomAD3 genomes AF: 0.000649 AC: 95 AN: 146304 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000976

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000543

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000790

Gnomad SAS AF: 0.00108

Gnomad FIN AF: 0.000545

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000469

Gnomad OTH AF: 0.00152

GnomAD4 exome AF: 0.0200 AC: 984 AN: 49166 Hom.: 0 Cov.: 0 AF XY: 0.0199 AC XY: 453 AN XY: 22732

Gnomad4 AFR exome AF: 0.0231

Gnomad4 AMR exome AF: 0.0259

Gnomad4 ASJ exome AF: 0.0197

Gnomad4 EAS exome AF: 0.0165

Gnomad4 SAS exome AF: 0.0290

Gnomad4 FIN exome AF: 0.00226

Gnomad4 NFE exome AF: 0.0199

Gnomad4 OTH exome AF: 0.0237

GnomAD4 genome AF: 0.000649 AC: 95 AN: 146368 Hom.: 0 Cov.: 31 AF XY: 0.000548 AC XY: 39 AN XY: 71166

Gnomad4 AFR AF: 0.000974

Gnomad4 AMR AF: 0.000543

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000792

Gnomad4 SAS AF: 0.00108

Gnomad4 FIN AF: 0.000545

Gnomad4 NFE AF: 0.000469

Gnomad4 OTH AF: 0.00151

ClinVar

Not reported in ClinVar

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;