rs4817788

Positions:

• chr21-36245332-T-C
• chr21-36245332-T-G
• chr21-36245332-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001320714.2(DOP1B):​c.3352T>C​(p.Cys1118Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C1118G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DOP1B NM_001320714.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056341946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOP1B	NM_001320714.2	c.3352T>C	p.Cys1118Arg	missense_variant	19/37	ENST00000691173.1	NP_001307643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOP1B	ENST00000691173.1	c.3352T>C	p.Cys1118Arg	missense_variant	19/37		NM_001320714.2	ENSP00000509598	P1
DOP1B	ENST00000399151.3	c.3352T>C	p.Cys1118Arg	missense_variant	19/37	1		ENSP00000382104	P1
DOP1B	ENST00000685394.1	c.3352T>C	p.Cys1118Arg	missense_variant, NMD_transcript_variant	19/35			ENSP00000510500
DOP1B	ENST00000693273.1	c.*2327T>C		3_prime_UTR_variant, NMD_transcript_variant	18/34			ENSP00000510799

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 120

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.79
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	0.96	P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.035
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.13	T
Polyphen		0.0010	B
Vest4		0.056
MutPred		0.14		Loss of stability (P = 0.0459);
MVP		0.14
MPC		0.31
ClinPred		0.16	T
GERP RS		2.5
Varity_R		0.18
gMVP		0.42

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: rs4817788; hg19: chr21-37617630;