rs2015343

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_000275.3(OCA2):c.1045-3508T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.603 (AC=91,581) in the gnomAD database across 151,994 control chromosomes, including 31,789 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.789. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 31789 hom., cov: 32)

Consequence

OCA2
NM_000275.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.502

Publications

3 publications found

Variant links:

Genes affected

OCA2 (HGNC:8101): (OCA2 melanosomal transmembrane protein) This gene encodes the human homolog of the mouse p (pink-eyed dilution) gene. The encoded protein is believed to be an integral membrane protein involved in small molecule transport, specifically tyrosine, which is a precursor to melanin synthesis. It is involved in mammalian pigmentation, where it may control skin color variation and act as a determinant of brown or blue eye color. Mutations in this gene result in type 2 oculocutaneous albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

OCA2 Gene-Disease associations (from GenCC):

oculocutaneous albinism type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
oculocutaneous albinism
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

OCA2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000275.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.7893 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000275.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.1045-3508T>C		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.1045-4489T>C		intron	N/A	NP_001287913.1	Q04671-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OCA2	ENST00000354638.8	TSL:1 MANE Select	c.1045-3508T>C	intron	N/A	ENSP00000346659.3	Q04671-1
OCA2	ENST00000353809.9	TSL:1	c.1045-4489T>C	intron	N/A	ENSP00000261276.8	Q04671-2
OCA2	ENST00000910120.1		c.1045-3508T>C	intron	N/A	ENSP00000580179.1	A0ACI8R8E8

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91582

AN:

151876

Hom.:

31794

Cov.:

show subpopulations

Gnomad AFR

AF:

0.274

Gnomad AMI

AF:

0.771

Gnomad AMR

AF:

0.573

Gnomad ASJ

AF:

0.716

Gnomad EAS

AF:

0.397

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.839

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.795

Gnomad OTH

AF:

0.639

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

GnomAD4 genome

AF:

0.603

AC:

91581

AN:

151994

Hom.:

31789

Cov.:

AF XY:

0.600

AC XY:

44567

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.274

AC:

11361

AN:

41450

American (AMR)

AF:

0.573

AC:

8741

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.716

AC:

2480

AN:

3466

East Asian (EAS)

AF:

0.397

AC:

2041

AN:

5142

South Asian (SAS)

AF:

0.370

AC:

1776

AN:

4794

European-Finnish (FIN)

AF:

0.839

AC:

8881

AN:

10586

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.795

AC:

54034

AN:

67972

Other (OTH)

AF:

0.633

AC:

1339

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1439

2878

4317

5756

7195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

718

1436

2154

2872

3590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.673

Hom.:

4940

Bravo

AF:

0.576

Asia WGS

AF:

0.457

AC:

1590

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.420

AC:

51538

AN:

122778

Turkish Variome

AF:

0.710

AC:

1097

AN:

1546

Hom.:

385

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.373

AC:

3338

AN:

8960

Hom.:

630

ABraOM SABE-WGS-1171

AF:

0.623

AC:

1459

AN:

2342

Hom.:

465

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

3.5

(source)

DANN

Benign

0.67

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over