Variant 2-23757585-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_017552.4(ATAD2B):c.3911C>T(p.Ser1304Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,460,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ATAD2B
NM_017552.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15890145).

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD2B	NM_017552.4 link	c.3911C>T	p.Ser1304Phe	missense_variant	25/28	ENST00000238789.10	NP_060022.2	Q9ULI0-1B3KWS5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATAD2B	ENST00000238789.10 link	c.3911C>T	p.Ser1304Phe	missense_variant	25/28	5	NM_017552.4	ENSP00000238789.5	Q9ULI0-1
ATAD2B	ENST00000381024.4 link	c.1736C>T	p.Ser579Phe	missense_variant	9/12	1		ENSP00000370412.4	H7BYF1
ATAD2B	ENST00000474583.5 link	n.3056C>T		non_coding_transcript_exon_variant	16/19	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000242

AC:

AN:

247692

Hom.:

AF XY:

0.0000372

AC XY:

AN XY:

134310

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1460826

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726662

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000331

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

The c.3911C>T (p.S1304F) alteration is located in exon 25 (coding exon 25) of the ATAD2B gene. This alteration results from a C to T substitution at nucleotide position 3911, causing the serine (S) at amino acid position 1304 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Benign

0.97

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Benign

0.67

M_CAP

Benign

0.033

MetaRNN

Benign

0.16

MetaSVM

Uncertain

-0.017

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.34

Sift

Uncertain

0.0050

Sift4G

Benign

0.095

Vest4

0.17

MVP

0.71

MPC

0.92

ClinPred

0.23

GERP RS

4.9

gMVP

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over