rs2070515

Variant names:

• chr21-36231355-A-G
• rs2070515
• NM_001320714.2:c.2350+221A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320714.2(DOP1B):​c.2350+221A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,148 control chromosomes in the GnomAD database, including 11,545 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (11545 hom., cov: 33)
• Consequence: DOP1B NM_001320714.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOP1B	NM_001320714.2	c.2350+221A>G		intron_variant	Intron 14 of 36	ENST00000691173.1	NP_001307643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOP1B	ENST00000691173.1	c.2350+221A>G		intron_variant	Intron 14 of 36		NM_001320714.2	ENSP00000509598.1
DOP1B	ENST00000399151.3	c.2350+221A>G		intron_variant	Intron 14 of 36	1		ENSP00000382104.3
DOP1B	ENST00000685394.1	n.2350+221A>G		intron_variant	Intron 14 of 34			ENSP00000510500.1
DOP1B	ENST00000693273.1	n.*1325+221A>G		intron_variant	Intron 13 of 33			ENSP00000510799.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54630 AN: 152030 Hom.: 11547 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.359 AC: 54614 AN: 152148 Hom.: 11545 Cov.: 33 AF XY: 0.357 AC XY: 26527 AN XY: 74350

African (AFR) AF: 0.130 AC: 5391 AN: 41532

American (AMR) AF: 0.392 AC: 6001 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1704 AN: 3472

East Asian (EAS) AF: 0.417 AC: 2159 AN: 5172

South Asian (SAS) AF: 0.494 AC: 2377 AN: 4808

European-Finnish (FIN) AF: 0.329 AC: 3477 AN: 10566

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32074 AN: 67994

Other (OTH) AF: 0.364 AC: 768 AN: 2110

Alfa AF: 0.440 Hom.: 29299

Bravo AF: 0.354

Asia WGS AF: 0.444 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.63
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2070515; hg19: chr21-37603653;