2-23757802-C-T

Variant names:

• chr2-23757802-C-T
• rs372393038
• NM_017552.4:c.3694G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017552.4(ATAD2B):​c.3694G>A​(p.Ala1232Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000705 in 1,418,926 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ATAD2B NM_017552.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.45

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19918731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATAD2B	NM_017552.4	c.3694G>A	p.Ala1232Thr	missense_variant	Exon 25 of 28	ENST00000238789.10	NP_060022.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATAD2B	ENST00000238789.10	c.3694G>A	p.Ala1232Thr	missense_variant	Exon 25 of 28	5	NM_017552.4	ENSP00000238789.5
ATAD2B	ENST00000381024.4	c.1519G>A	p.Ala507Thr	missense_variant	Exon 9 of 12	1		ENSP00000370412.4
ATAD2B	ENST00000474583.5	n.2839G>A		non_coding_transcript_exon_variant	Exon 16 of 19	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1418926 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 703376

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.12e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.65	D
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.20	T
MetaSVM	Uncertain	-0.0033	T
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.87	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.022	D
Sift4G	Benign	0.24	T
Vest4		0.24
MutPred		0.069		Loss of loop (P = 0.0374);
MVP		0.66
MPC		0.67
ClinPred		0.64	D
GERP RS		5.2
gMVP		0.15

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: rs372393038; hg19: chr2-23980672;