chr2-23757889-T-A

Variant names:

• chr2-23757889-T-A
• rs201429059
• NM_017552.4:c.3607A>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.3607A>T​(p.Met1203Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,942 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. M1203V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ATAD2B NM_017552.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.907
• 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=0.08050537).

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.3607A>T	p.Met1203Leu	missense	Exon 25 of 28	NP_060022.2	Q9ULI0-1
	ATAD2B	NM_001354107.2		c.3634A>T	p.Met1212Leu	missense	Exon 26 of 29	NP_001341036.1
	ATAD2B	NM_001242338.3		c.3592A>T	p.Met1198Leu	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.3607A>T	p.Met1203Leu	missense	Exon 25 of 28	ENSP00000238789.5	Q9ULI0-1
	ATAD2B	ENST00000381024.4	TSL:1	c.1432A>T	p.Met478Leu	missense	Exon 9 of 12	ENSP00000370412.4	H7BYF1
	ATAD2B	ENST00000925212.1		c.3592A>T	p.Met1198Leu	missense	Exon 25 of 28	ENSP00000595271.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448942 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720486

African (AFR) AF: 0.00 AC: 0 AN: 32352

American (AMR) AF: 0.00 AC: 0 AN: 41470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25468

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 83024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108442

Other (OTH) AF: 0.00 AC: 0 AN: 59740

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	14
DANN	Benign	0.83
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.33	N
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.71	T
PhyloP100		0.91
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.25
Sift	Benign	0.68	T
Sift4G	Benign	0.89	T
Vest4		0.16
MutPred		0.22		Gain of glycosylation at S1202 (P = 0.0464)
MVP		0.68
MPC		0.45
ClinPred		0.051	T
GERP RS		3.1
gMVP		0.11
Mutation Taster		=88/12	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: rs201429059; hg19: chr2-23980759;