rs1800407

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBA1

The NM_000275.3(OCA2):c.1256G>A(p.Arg419Gln) variant causes a missense change. The variant allele was found at a frequency of 0.068 in 1,613,592 control chromosomes in the GnomAD database, including 4,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R419W) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.049 ( 241 hom., cov: 32)

Exomes 𝑓: 0.070 ( 4169 hom. )

Consequence

OCA2
NM_000275.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 7.14

Publications

154 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, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, ClinGen

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.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr15-27985173-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 194160.

BP4

Computational evidence support a benign effect (MetaRNN=0.0110088885).

BP6

Variant 15-27985172-C-T is Benign according to our data. Variant chr15-27985172-C-T is described in ClinVar as Benign. ClinVar VariationId is 963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.1256G>A	p.Arg419Gln	missense	Exon 13 of 24	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.1184G>A	p.Arg395Gln	missense	Exon 12 of 23	NP_001287913.1	Q04671-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OCA2	ENST00000354638.8	TSL:1 MANE Select	c.1256G>A	p.Arg419Gln	missense	Exon 13 of 24	ENSP00000346659.3	Q04671-1
OCA2	ENST00000353809.9	TSL:1	c.1184G>A	p.Arg395Gln	missense	Exon 12 of 23	ENSP00000261276.8	Q04671-2
OCA2	ENST00000910120.1		c.1256G>A	p.Arg419Gln	missense	Exon 13 of 26	ENSP00000580179.1

Frequencies

GnomAD3 genomes

AF:

0.0486

AC:

7402

AN:

152172

Hom.:

241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0671

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0313

Gnomad FIN

AF:

0.0429

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0709

Gnomad OTH

AF:

0.0512

GnomAD2 exomes

AF:

0.0469

AC:

11577

AN:

246792

AF XY:

0.0485

show subpopulations

Gnomad AFR exome

AF:

0.0114

Gnomad AMR exome

AF:

0.0436

Gnomad ASJ exome

AF:

0.0492

Gnomad EAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.0441

Gnomad NFE exome

AF:

0.0648

Gnomad OTH exome

AF:

0.0559

GnomAD4 exome

AF:

0.0700

AC:

102342

AN:

1461302

Hom.:

4169

Cov.:

AF XY:

0.0689

AC XY:

50090

AN XY:

726900

show subpopulations

African (AFR)

AF:

0.0110

AC:

369

AN:

33476

American (AMR)

AF:

0.0457

AC:

2043

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0496

AC:

1296

AN:

26128

East Asian (EAS)

AF:

0.000403

AC:

AN:

39698

South Asian (SAS)

AF:

0.0313

AC:

2698

AN:

86232

European-Finnish (FIN)

AF:

0.0434

AC:

2303

AN:

53094

Middle Eastern (MID)

AF:

0.0336

AC:

194

AN:

5768

European-Non Finnish (NFE)

AF:

0.0803

AC:

89250

AN:

1111814

Other (OTH)

AF:

0.0691

AC:

4173

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

5590

11179

16769

22358

27948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3344

6688

10032

13376

16720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0486

AC:

7403

AN:

152290

Hom.:

241

Cov.:

AF XY:

0.0474

AC XY:

3528

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0141

AC:

585

AN:

41576

American (AMR)

AF:

0.0670

AC:

1025

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0493

AC:

171

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5180

South Asian (SAS)

AF:

0.0315

AC:

152

AN:

4826

European-Finnish (FIN)

AF:

0.0429

AC:

455

AN:

10602

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0710

AC:

4827

AN:

68018

Other (OTH)

AF:

0.0502

AC:

106

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

340

679

1019

1358

1698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0623

Hom.:

1147

Bravo

AF:

0.0480

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0730

EpiControl

AF:

0.0708

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Tyrosinase-positive oculocutaneous albinism (1)

SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.57

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.41

MutationAssessor

Benign

1.5

PhyloP100

7.1

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.57

Sift

Benign

0.094

Sift4G

Benign

0.11

Varity_R

0.21

gMVP

0.82

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over