2-66821463-T-C

Variant names:

• chr2-66821463-T-C
• rs1106577
• ENST00000455096.1:n.786A>G

Variant summary

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

The ENST00000455096.1(DNMT3AP1):​n.786A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,080 control chromosomes in the GnomAD database, including 21,747 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 0.53 (21729 hom., cov: 32)
  • Exomes 𝑓: 0.54 (18 hom.)
• Consequence: DNMT3AP1 ENST00000455096.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354
• Publications: 7 publications found

Genes affected

DNMT3AP1 (HGNC:23164): (DNA methyltransferase 3A pseudogene 1)

LINC01798 (HGNC:52588): (long intergenic non-protein coding RNA 1798)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNMT3AP1		n.66821463T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNMT3AP1	ENST00000455096.1	n.786A>G		non_coding_transcript_exon_variant	Exon 2 of 2	6
LINC01798	ENST00000715601.1	n.185-26523T>C		intron_variant	Intron 2 of 6
LINC01798	ENST00000758432.1	n.185-26523T>C		intron_variant	Intron 2 of 5

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80732 AN: 151852 Hom.: 21696 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.488

GnomAD4 exome AF: 0.537 AC: 58 AN: 108 Hom.: 18 Cov.: 0 AF XY: 0.541 AC XY: 40 AN XY: 74

African (AFR) AF: 0.500 AC: 2 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.533 AC: 16 AN: 30

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.563 AC: 36 AN: 64

Other (OTH) AF: 0.375 AC: 3 AN: 8

GnomAD4 genome AF: 0.532 AC: 80817 AN: 151972 Hom.: 21729 Cov.: 32 AF XY: 0.538 AC XY: 39947 AN XY: 74258

African (AFR) AF: 0.586 AC: 24323 AN: 41494

American (AMR) AF: 0.601 AC: 9179 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1478 AN: 3470

East Asian (EAS) AF: 0.606 AC: 3115 AN: 5140

South Asian (SAS) AF: 0.646 AC: 3102 AN: 4800

European-Finnish (FIN) AF: 0.533 AC: 5619 AN: 10542

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32329 AN: 67930

Other (OTH) AF: 0.491 AC: 1036 AN: 2112

Alfa AF: 0.516 Hom.: 8860

Bravo AF: 0.537

Asia WGS AF: 0.620 AC: 2155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.5
DANN	Benign	0.66
PhyloP100		0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1106577; hg19: chr2-67048595;