rs765383233

Variant names:

• chr2-23757534-G-A
• rs765383233
• NM_017552.4:c.3962C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-23757534-G-A
• chr2-23757534-G-C

Variant summary

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

The NM_017552.4(ATAD2B):​c.3962C>T​(p.Ser1321Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000439 in 1,593,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: ATAD2B NM_017552.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.717
• Publications: 3 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=0.047993004).
• BS2: High AC in GnomAd4 at 8 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.3962C>T	p.Ser1321Leu	missense	Exon 25 of 28	NP_060022.2	Q9ULI0-1
	ATAD2B	NM_001354107.2		c.3989C>T	p.Ser1330Leu	missense	Exon 26 of 29	NP_001341036.1
	ATAD2B	NM_001242338.3		c.3947C>T	p.Ser1316Leu	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.3962C>T	p.Ser1321Leu	missense	Exon 25 of 28	ENSP00000238789.5	Q9ULI0-1
	ATAD2B	ENST00000381024.4	TSL:1	c.1787C>T	p.Ser596Leu	missense	Exon 9 of 12	ENSP00000370412.4	H7BYF1
	ATAD2B	ENST00000925212.1		c.3947C>T	p.Ser1316Leu	missense	Exon 25 of 28	ENSP00000595271.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152032 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000390 AC: 9 AN: 230832 AF XY: 0.0000719

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000335

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000594

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000465

Gnomad OTH exome AF: 0.000182

GnomAD4 exome AF: 0.0000430 AC: 62 AN: 1441320 Hom.: 0 Cov.: 31 AF XY: 0.0000447 AC XY: 32 AN XY: 716374

African (AFR) AF: 0.00 AC: 0 AN: 31902

American (AMR) AF: 0.0000252 AC: 1 AN: 39704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25024

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39450

South Asian (SAS) AF: 0.0000487 AC: 4 AN: 82068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 0.0000498 AC: 55 AN: 1105128

Other (OTH) AF: 0.0000168 AC: 1 AN: 59468

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152032 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74264

African (AFR) AF: 0.00 AC: 0 AN: 41376

American (AMR) AF: 0.0000655 AC: 1 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000762 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.0000497 AC: 6

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	0.068
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Benign	0.67
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.29	N
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.52	T
PhyloP100		0.72
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.17
Sift	Benign	0.72	T
Sift4G	Benign	0.48	T
Vest4		0.092
MVP		0.32
MPC		0.44
ClinPred		0.033	T
GERP RS		2.5
gMVP		0.14
Mutation Taster		=95/5	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

Other links and lift over

dbSNP: rs765383233; hg19: chr2-23980404; COSMIC: COSV53196387; COSMIC: COSV53196387;