Genetic Variant NM_017552.4:c.4274C>A (chr2-23754240-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_017552.4(ATAD2B):c.4274C>A(p.Ser1425Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000212 in 1,412,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ATAD2B
NM_017552.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.29

Publications

0 publications found

Variant links:

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]

ATAD2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.797

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATAD2B	NM_017552.4	MANE Select	c.4274C>A	p.Ser1425Tyr	missense	Exon 27 of 28	NP_060022.2	Q9ULI0-1
ATAD2B	NM_001354107.2		c.4301C>A	p.Ser1434Tyr	missense	Exon 28 of 29	NP_001341036.1
ATAD2B	NM_001242338.3		c.4259C>A	p.Ser1420Tyr	missense	Exon 27 of 28	NP_001229267.2	Q9ULI0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATAD2B	ENST00000238789.10	TSL:5 MANE Select	c.4274C>A	p.Ser1425Tyr	missense	Exon 27 of 28	ENSP00000238789.5	Q9ULI0-1
ATAD2B	ENST00000381024.4	TSL:1	c.2099C>A	p.Ser700Tyr	missense	Exon 11 of 12	ENSP00000370412.4	H7BYF1
ATAD2B	ENST00000925212.1		c.4220C>A	p.Ser1407Tyr	missense	Exon 27 of 28	ENSP00000595271.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

184048

AF XY:

0.0000102

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000114

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:

0.00000212

AC:

AN:

1412444

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32292

American (AMR)

AF:

0.0000801

AC:

AN:

37456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25332

East Asian (EAS)

AF:

0.00

AC:

AN:

37860

South Asian (SAS)

AF:

0.00

AC:

AN:

79488

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50726

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1085032

Other (OTH)

AF:

0.00

AC:

AN:

58568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.39

CADD

Uncertain

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.98

M_CAP

Pathogenic

0.48

MetaRNN

Pathogenic

0.80

MetaSVM

Pathogenic

0.84

PhyloP100

6.3

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.0

REVEL

Pathogenic

0.81

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Vest4

0.74

MutPred

0.44

Loss of disorder (P = 0.1102)

MVP

0.98

MPC

1.3

ClinPred

0.89

GERP RS

4.7

gMVP

0.62

Mutation Taster

=40/60

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over