Genetic Variant OCA2:c.1784+93G>A (chr15-27957495-C-T) – ACMG Classification: Benign (-20 pts)

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.1784+93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 1,409,974 control chromosomes in the GnomAD database, including 3,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 247 hom., cov: 33)

Exomes 𝑓: 0.061 ( 3039 hom. )

Consequence

OCA2
NM_000275.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0670

Publications

2 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 (BayesDel_noAF=-0.88).

BP6

Variant 15-27957495-C-T is Benign according to our data. Variant chr15-27957495-C-T is described in ClinVar as Benign. ClinVar VariationId is 1226185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.12 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.1784+93G>A		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.1712+93G>A		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.1784+93G>A	intron	N/A	ENSP00000346659.3	Q04671-1
OCA2	ENST00000353809.9	TSL:1	c.1712+93G>A	intron	N/A	ENSP00000261276.8	Q04671-2
OCA2	ENST00000910120.1		c.1784+93G>A	intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes

AF:

0.0464

AC:

7060

AN:

152152

Hom.:

247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.0624

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.00771

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0271

Gnomad MID

AF:

0.0860

Gnomad NFE

AF:

0.0581

Gnomad OTH

AF:

0.0660

GnomAD4 exome

AF:

0.0615

AC:

77341

AN:

1257704

Hom.:

3039

AF XY:

0.0644

AC XY:

40810

AN XY:

633790

show subpopulations

African (AFR)

AF:

0.00878

AC:

260

AN:

29596

American (AMR)

AF:

0.0373

AC:

1653

AN:

44304

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

3752

AN:

24790

East Asian (EAS)

AF:

0.00471

AC:

182

AN:

38618

South Asian (SAS)

AF:

0.127

AC:

10453

AN:

82006

European-Finnish (FIN)

AF:

0.0316

AC:

1558

AN:

49310

Middle Eastern (MID)

AF:

0.124

AC:

472

AN:

3802

European-Non Finnish (NFE)

AF:

0.0595

AC:

55479

AN:

931678

Other (OTH)

AF:

0.0659

AC:

3532

AN:

53600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

3830

7660

11489

15319

19149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1964

3928

5892

7856

9820

<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:

0.0463

AC:

7056

AN:

152270

Hom.:

247

Cov.:

AF XY:

0.0476

AC XY:

3545

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0104

AC:

431

AN:

41566

American (AMR)

AF:

0.0623

AC:

953

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

491

AN:

3466

East Asian (EAS)

AF:

0.00773

AC:

AN:

5174

South Asian (SAS)

AF:

0.129

AC:

620

AN:

4822

European-Finnish (FIN)

AF:

0.0271

AC:

288

AN:

10614

Middle Eastern (MID)

AF:

0.0822

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0581

AC:

3954

AN:

68014

Other (OTH)

AF:

0.0653

AC:

138

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

357

713

1070

1426

1783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0483

Hom.:

Bravo

AF:

0.0452

Asia WGS

AF:

0.0500

AC:

173

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.1

(source)

DANN

Benign

0.47

PhyloP100

-0.067

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

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