rs1800401

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000275.3(OCA2):c.913C>T(p.Arg305Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0579 in 1,614,008 control chromosomes in the GnomAD database, including 3,680 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. R305Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.077 ( 587 hom., cov: 32)

Exomes 𝑓: 0.056 ( 3093 hom. )

Consequence

OCA2
NM_000275.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 5.50

Publications

63 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: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

OCA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020300746).

BP6

Variant 15-28014907-G-A is Benign according to our data. Variant chr15-28014907-G-A is described in ClinVar as Benign. ClinVar VariationId is 962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 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.913C>T	p.Arg305Trp	missense	Exon 9 of 24	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.913C>T	p.Arg305Trp	missense	Exon 9 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.913C>T	p.Arg305Trp	missense	Exon 9 of 24	ENSP00000346659.3	Q04671-1
OCA2	ENST00000353809.9	TSL:1	c.913C>T	p.Arg305Trp	missense	Exon 9 of 23	ENSP00000261276.8	Q04671-2
OCA2	ENST00000910120.1		c.913C>T	p.Arg305Trp	missense	Exon 9 of 26	ENSP00000580179.1

Frequencies

GnomAD3 genomes

AF:

0.0769

AC:

11696

AN:

152100

Hom.:

584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.0625

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.00828

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.0309

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0490

Gnomad OTH

AF:

0.0793

GnomAD2 exomes

AF:

0.0632

AC:

15874

AN:

250992

AF XY:

0.0671

show subpopulations

Gnomad AFR exome

AF:

0.137

Gnomad AMR exome

AF:

0.0352

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.00636

Gnomad FIN exome

AF:

0.0341

Gnomad NFE exome

AF:

0.0506

Gnomad OTH exome

AF:

0.0667

GnomAD4 exome

AF:

0.0559

AC:

81773

AN:

1461790

Hom.:

3093

Cov.:

AF XY:

0.0583

AC XY:

42409

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.139

AC:

4664

AN:

33478

American (AMR)

AF:

0.0374

AC:

1671

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

3945

AN:

26130

East Asian (EAS)

AF:

0.00453

AC:

180

AN:

39700

South Asian (SAS)

AF:

0.130

AC:

11186

AN:

86238

European-Finnish (FIN)

AF:

0.0329

AC:

1755

AN:

53402

Middle Eastern (MID)

AF:

0.123

AC:

711

AN:

5768

European-Non Finnish (NFE)

AF:

0.0483

AC:

53741

AN:

1111960

Other (OTH)

AF:

0.0649

AC:

3920

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

4564

9129

13693

18258

22822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2102

4204

6306

8408

10510

<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:

0.0769

AC:

11707

AN:

152218

Hom.:

587

Cov.:

AF XY:

0.0762

AC XY:

5670

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.136

AC:

5631

AN:

41502

American (AMR)

AF:

0.0623

AC:

953

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

471

AN:

3472

East Asian (EAS)

AF:

0.00830

AC:

AN:

5182

South Asian (SAS)

AF:

0.135

AC:

652

AN:

4830

European-Finnish (FIN)

AF:

0.0309

AC:

328

AN:

10612

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0490

AC:

3330

AN:

68008

Other (OTH)

AF:

0.0785

AC:

166

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

532

1064

1597

2129

2661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0621

Hom.:

889

Bravo

AF:

0.0796

TwinsUK

AF:

0.0499

AC:

185

ALSPAC

AF:

0.0576

AC:

222

ESP6500AA

AF:

0.134

AC:

590

ESP6500EA

AF:

0.0495

AC:

426

ExAC

AF:

0.0648

AC:

7861

Asia WGS

AF:

0.0570

AC:

197

AN:

3478

EpiCase

AF:

0.0574

EpiControl

AF:

0.0610

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Tyrosinase-positive oculocutaneous albinism (2)

Tyrosinase-positive oculocutaneous albinism;C1856895:SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES (1)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.75

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.4

PhyloP100

5.5

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.32

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

0.95

Vest4

0.27

MPC

0.094

ClinPred

0.046

GERP RS

3.7

Varity_R

0.22

gMVP

0.48

Mutation Taster

=97/3

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

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