2-23757702-C-A

Variant names:

• chr2-23757702-C-A
• rs369011855
• NM_017552.4:c.3794G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017552.4(ATAD2B):​c.3794G>T​(p.Gly1265Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ATAD2B NM_017552.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13604593).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017552.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATAD2B	NM_017552.4	MANE Select	c.3794G>T	p.Gly1265Val	missense	Exon 25 of 28	NP_060022.2	Q9ULI0-1
	ATAD2B	NM_001354107.2		c.3821G>T	p.Gly1274Val	missense	Exon 26 of 29	NP_001341036.1
	ATAD2B	NM_001242338.3		c.3779G>T	p.Gly1260Val	missense	Exon 25 of 28	NP_001229267.2	Q9ULI0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATAD2B	ENST00000238789.10	TSL:5 MANE Select	c.3794G>T	p.Gly1265Val	missense	Exon 25 of 28	ENSP00000238789.5	Q9ULI0-1
	ATAD2B	ENST00000381024.4	TSL:1	c.1619G>T	p.Gly540Val	missense	Exon 9 of 12	ENSP00000370412.4	H7BYF1
	ATAD2B	ENST00000925212.1		c.3779G>T	p.Gly1260Val	missense	Exon 25 of 28	ENSP00000595271.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Benign	0.96
Eigen	Benign	0.069
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.32	N
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.14	T
MetaSVM	Uncertain	-0.20	T
PhyloP100		2.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.26
Sift	Benign	0.044	D
Sift4G	Benign	0.28	T
Vest4		0.23
MVP		0.59
MPC		0.69
ClinPred		0.29	T
GERP RS		3.9
gMVP		0.37
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs369011855; hg19: chr2-23980572;