12-49019797-TAAA-TA

Variant names:

• chr12-49019797-TAA-T
• NM_003482.4:c.*1981_*1982delTT

Variant summary

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

The NM_003482.4(KMT2D):​c.*1981_*1982delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000489 in 51,140 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 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00049 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KMT2D NM_003482.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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_exome allele frequency = 0.000489 (25/51140) while in subpopulation SAS AF= 0.00233 (1/430). AF 95% confidence interval is 0.000296. There are 0 homozygotes in gnomad4_exome. There are 11 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2D	NM_003482.4	c.*1981_*1982delTT		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.*1981_*1982delTT		3_prime_UTR_variant	Exon 55 of 55	5	NM_003482.4	ENSP00000301067.7
ENSG00000288710	ENST00000683988.1	n.*76+1905_*76+1906delTT		intron_variant	Intron 5 of 15			ENSP00000506939.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 146356 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000489 AC: 25 AN: 51140 Hom.: 0 AF XY: 0.000464 AC XY: 11 AN XY: 23694

Gnomad4 AFR exome AF: 0.000409

Gnomad4 AMR exome AF: 0.000661

Gnomad4 ASJ exome AF: 0.00122

Gnomad4 EAS exome AF: 0.000413

Gnomad4 SAS exome AF: 0.00233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000480

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 146356 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 71120

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-49413580;