2-23754682-C-T

Variant names:

• chr2-23754682-C-T
• rs200259678
• NM_017552.4:c.4171G>A

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.4171G>A​(p.Val1391Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1391L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ATAD2B NM_017552.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517
• 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=0.09371355).

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.4171G>A	p.Val1391Met	missense	Exon 26 of 28	NP_060022.2	Q9ULI0-1
	ATAD2B	NM_001354107.2		c.4198G>A	p.Val1400Met	missense	Exon 27 of 29	NP_001341036.1
	ATAD2B	NM_001242338.3		c.4156G>A	p.Val1386Met	missense	Exon 26 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.4171G>A	p.Val1391Met	missense	Exon 26 of 28	ENSP00000238789.5	Q9ULI0-1
	ATAD2B	ENST00000381024.4	TSL:1	c.1996G>A	p.Val666Met	missense	Exon 10 of 12	ENSP00000370412.4	H7BYF1
	ATAD2B	ENST00000925212.1		c.4117G>A	p.Val1373Met	missense	Exon 26 of 28	ENSP00000595271.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000805 AC: 2 AN: 248464 AF XY: 0.00

Gnomad AFR exome AF: 0.0000648

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460802 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726680

African (AFR) AF: 0.0000599 AC: 2 AN: 33414

American (AMR) AF: 0.0000224 AC: 1 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111322

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	18
DANN	Uncertain	1.0
Eigen	Benign	-0.18
Eigen_PC	Benign	0.029
FATHMM_MKL	Benign	0.50	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.51	T
PhyloP100		0.52
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.26
Sift	Benign	0.061	T
Sift4G	Benign	0.13	T
Vest4		0.24
MutPred		0.12		Gain of glycosylation at P1390 (P = 0.1012)
MVP		0.66
MPC		0.48
ClinPred		0.47	T
GERP RS		4.5
gMVP		0.070
Mutation Taster		=97/3	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: rs200259678; hg19: chr2-23977552; COSMIC: COSV108775641;