chr2-23757868-A-G

Position:

• chr2-23757868-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017552.4(ATAD2B):​c.3628T>C​(p.Cys1210Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,441,252 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ATAD2B NM_017552.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.43

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD2B	NM_017552.4	c.3628T>C	p.Cys1210Arg	missense_variant	25/28	ENST00000238789.10	NP_060022.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATAD2B	ENST00000238789.10	c.3628T>C	p.Cys1210Arg	missense_variant	25/28	5	NM_017552.4	ENSP00000238789.5
ATAD2B	ENST00000381024.4	c.1453T>C	p.Cys485Arg	missense_variant	9/12	1		ENSP00000370412.4
ATAD2B	ENST00000474583.5	n.2773T>C		non_coding_transcript_exon_variant	16/19	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441252 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 716390

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.3628T>C (p.C1210R) alteration is located in exon 25 (coding exon 25) of the ATAD2B gene. This alteration results from a T to C substitution at nucleotide position 3628, causing the cysteine (C) at amino acid position 1210 to be replaced by an arginine (R). 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	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.70	D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	0.37	D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.055	T
Vest4		0.76
MutPred		0.14		Loss of helix (P = 0.0072);
MVP		0.90
MPC		1.8
ClinPred		0.94	D
GERP RS		5.6
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-23980738;