rs374521897

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-23758006-T-A
• chr2-23758006-T-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_017552.4(ATAD2B):​c.3490A>T​(p.Thr1164Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,611,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: ATAD2B NM_017552.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.047522545).
• BS2: High AC in GnomAd4 at 10 AD gene.

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>T	p.Thr1164Ser	missense	Exon 25 of 28	NP_060022.2	Q9ULI0-1
	ATAD2B	NM_001354107.2		c.3517A>T	p.Thr1173Ser	missense	Exon 26 of 29	NP_001341036.1
	ATAD2B	NM_001242338.3		c.3475A>T	p.Thr1159Ser	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>T	p.Thr1164Ser	missense	Exon 25 of 28	ENSP00000238789.5	Q9ULI0-1
	ATAD2B	ENST00000381024.4	TSL:1	c.1315A>T	p.Thr439Ser	missense	Exon 9 of 12	ENSP00000370412.4	H7BYF1
	ATAD2B	ENST00000925212.1		c.3475A>T	p.Thr1159Ser	missense	Exon 25 of 28	ENSP00000595271.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000117 AC: 29 AN: 247742 AF XY: 0.0000967

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.0000584

Gnomad ASJ exome AF: 0.0000997

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.000205

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000209 AC: 305 AN: 1459552 Hom.: 0 Cov.: 31 AF XY: 0.000190 AC XY: 138 AN XY: 726046

African (AFR) AF: 0.000120 AC: 4 AN: 33322

American (AMR) AF: 0.0000225 AC: 1 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 85722

European-Finnish (FIN) AF: 0.0000376 AC: 2 AN: 53210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000262 AC: 291 AN: 1110938

Other (OTH) AF: 0.0000498 AC: 3 AN: 60288

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74326

African (AFR) AF: 0.0000241 AC: 1 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000677 Hom.: 0

Bravo AF: 0.0000680

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.0000745 AC: 9

EpiCase AF: 0.000273

EpiControl AF: 0.000357

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.86
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.31	N
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.59	T
PhyloP100		1.8
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.25
Sift	Benign	0.45	T
Sift4G	Benign	0.67	T
Vest4		0.059
MutPred		0.088		Gain of phosphorylation at T1164 (P = 0.0587)
MVP		0.34
MPC		0.43
ClinPred		0.026	T
GERP RS		3.0
gMVP		0.20
Mutation Taster		=92/8	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;