ATAD2 p.Asp1207Glu

Variant names:

• chr8-123328437-G-T
• NM_014109.4:c.3621C>A
• ATAD2 p.Asp1207Glu

Your query was ambiguous. Multiple possible variants found:

• chr8-123328437-G-T
• chr8-123328437-G-C

Variant summary

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

The NM_014109.4(ATAD2):​c.3621C>A​(p.Asp1207Glu) 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. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATAD2 NM_014109.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635
• Publications: 0 publications found

Genes affected

ATAD2 (HGNC:30123): (ATPase family AAA domain containing 2) A large family of ATPases has been described, whose key feature is that they share a conserved region of about 220 amino acids that contains an ATP-binding site. The proteins that belong to this family either contain one or two AAA (ATPases Associated with diverse cellular Activities) domains. AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes. The protein encoded by this gene contains two AAA domains, as well as a bromodomain. [provided by RefSeq, Jul 2008]

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=0.03224638).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014109.4. 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
	ATAD2	NM_014109.4	MANE Select	c.3621C>A	p.Asp1207Glu	missense	Exon 25 of 28	NP_054828.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATAD2	ENST00000287394.10	TSL:1 MANE Select	c.3621C>A	p.Asp1207Glu	missense	Exon 25 of 28	ENSP00000287394.5	Q6PL18-1
	ATAD2	ENST00000521903.5	TSL:1	c.1575C>A	p.Asp525Glu	missense	Exon 26 of 29	ENSP00000429213.1	A0A0B4J211
	ATAD2	ENST00000519124.5	TSL:1	n.*3431C>A		non_coding_transcript_exon	Exon 25 of 28	ENSP00000429617.1	E5RHW7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.32
DANN	Benign	0.95
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.64
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.069
Sift	Benign	0.58	T
Sift4G	Benign	0.69	T
Varity_R		0.022
gMVP		0.11
Mutation Taster		=89/11	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-124340677;

COSMIC: COSV54879844;