2-23900669-C-T

Position:

• chr2-23900669-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017552.4(ATAD2B):​c.217-4699G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,022 control chromosomes in the GnomAD database, including 13,693 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 0.41 (13691 hom., cov: 31)
  • Exomes 𝑓: 0.36 (2 hom.)
• Consequence: ATAD2B NM_017552.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

Genes affected

ATAD2B (HGNC:29230): (ATPase family AAA domain containing 2B) The protein encoded by this gene belongs to the AAA ATPase family. This family member includes an N-terminal bromodomain. It has been found to be localized to the nucleus, partly to replication sites, consistent with a chromatin-related function. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2014]

RPS13P4 (HGNC:35731): (ribosomal protein S13 pseudogene 4)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATAD2B	NM_017552.4	c.217-4699G>A		intron_variant		ENST00000238789.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATAD2B	ENST00000238789.10	c.217-4699G>A		intron_variant		5	NM_017552.4	P1
ATAD2B	ENST00000439915.1	c.217-4699G>A		intron_variant		1
RPS13P4	ENST00000421721.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61771 AN: 151882 Hom.: 13675 Cov.: 31

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.439

GnomAD4 exome AF: 0.364 AC: 8 AN: 22 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 8 AN XY: 16

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.333

GnomAD4 genome AF: 0.407 AC: 61806 AN: 152000 Hom.: 13691 Cov.: 31 AF XY: 0.414 AC XY: 30777 AN XY: 74260

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.444

Alfa AF: 0.435 Hom.: 2709

Bravo AF: 0.415

Asia WGS AF: 0.603 AC: 2093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.76

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: rs17711796; hg19: chr2-24123539;