chr2-23758006-T-G

Variant names:

• chr2-23758006-T-G
• rs374521897
• NM_017552.4:c.3490A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017552.4(ATAD2B):​c.3490A>C​(p.Thr1164Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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. T1164S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATAD2B NM_017552.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06792867).

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.3490A>C	p.Thr1164Pro	missense	Exon 25 of 28	NP_060022.2	Q9ULI0-1
	ATAD2B	NM_001354107.2		c.3517A>C	p.Thr1173Pro	missense	Exon 26 of 29	NP_001341036.1
	ATAD2B	NM_001242338.3		c.3475A>C	p.Thr1159Pro	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.3490A>C	p.Thr1164Pro	missense	Exon 25 of 28	ENSP00000238789.5	Q9ULI0-1
	ATAD2B	ENST00000381024.4	TSL:1	c.1315A>C	p.Thr439Pro	missense	Exon 9 of 12	ENSP00000370412.4	H7BYF1
	ATAD2B	ENST00000925212.1		c.3475A>C	p.Thr1159Pro	missense	Exon 25 of 28	ENSP00000595271.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Benign	0.97
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.35	N
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.38	T
PhyloP100		1.8
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.060	N
REVEL	Uncertain	0.32
Sift	Benign	0.16	T
Sift4G	Benign	0.22	T
Vest4		0.093
MutPred		0.099		Gain of helix (P = 0.0854)
MVP		0.38
MPC		0.63
ClinPred		0.17	T
GERP RS		3.0
gMVP		0.33
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs374521897; hg19: chr2-23980876;