6-83130270-A-T

Position:

• chr6-83130270-A-T

Variant summary

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

The NM_015018.4(DOP1A):​c.2489A>T​(p.Glu830Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DOP1A NM_015018.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95

Genes affected

DOP1A (HGNC:21194): (DOP1 leucine zipper like protein A) Predicted to be involved in Golgi to endosome transport and endoplasmic reticulum organization. Predicted to be located in Golgi membrane. Predicted to be active in endosome and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

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
DOP1A	NM_015018.4	c.2489A>T	p.Glu830Val	missense_variant	17/39	ENST00000349129.7	NP_055833.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOP1A	ENST00000349129.7	c.2489A>T	p.Glu830Val	missense_variant	17/39	1	NM_015018.4	ENSP00000195654	P4
DOP1A	ENST00000369739.7	c.2462A>T	p.Glu821Val	missense_variant	16/39	1		ENSP00000358754	A1
DOP1A	ENST00000237163.9	c.2462A>T	p.Glu821Val	missense_variant	17/40	5		ENSP00000237163	A1
DOP1A	ENST00000493541.1	n.57A>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

May 02, 2024

The c.2462A>T (p.E821V) alteration is located in exon 17 (coding exon 15) of the DOPEY1 gene. This alteration results from a A to T substitution at nucleotide position 2462, causing the glutamic acid (E) at amino acid position 821 to be replaced by a valine (V). 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	Uncertain	0.35
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	.;T;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;.
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	.;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.6	.;D;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.0070	.;D;.
Sift4G	Uncertain	0.018	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.81
MutPred		0.36		.;Loss of disorder (P = 0.0347);.;
MVP		0.10
MPC		0.83
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.43
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr6-83839989;