21-36164777-G-A

Position:

• chr21-36164777-G-A

Variant summary

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

The NM_001320714.2(DOP1B):​c.44G>A​(p.Arg15Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DOP1B NM_001320714.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.45

Genes affected

DOP1B (HGNC:1291): (DOP1 leucine zipper like protein B) Involved in cognition. Located in early endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

DOP1B (HGNC:):

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
DOP1B	NM_001320714.2	c.44G>A	p.Arg15Lys	missense_variant	2/37	ENST00000691173.1	NP_001307643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOP1B	ENST00000691173.1	c.44G>A	p.Arg15Lys	missense_variant	2/37		NM_001320714.2	ENSP00000509598.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Oct 29, 2024

The c.44G>A (p.R15K) alteration is located in exon 2 (coding exon 1) of the DOPEY2 gene. This alteration results from a G to A substitution at nucleotide position 44, causing the arginine (R) at amino acid position 15 to be replaced by a lysine (K). 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	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	.;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.7	D;N
REVEL	Benign	0.20
Sift	Benign	0.18	T;D
Sift4G	Benign	0.23	T;D
Polyphen		0.96	.;D
Vest4		0.17
MutPred		0.80		Gain of ubiquitination at R15 (P = 0.0155);Gain of ubiquitination at R15 (P = 0.0155);
MVP		0.29
MPC		0.21
ClinPred		0.96	D
GERP RS		3.0
Varity_R		0.61
gMVP		0.45

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

Other links and lift over

dbSNP: rs1349902608; hg19: chr21-37537075;