Genetic Variant OCA2:c.228-14869A>G (chr15-28047032-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000275.3(OCA2):c.228-14869A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,992 control chromosomes in the GnomAD database, including 9,018 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 0.29 ( 9018 hom., cov: 32)

Consequence

OCA2
NM_000275.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.712

Publications

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

OCA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3 link	c.228-14869A>G		intron_variant	Intron 2 of 23	ENST00000354638.8	NP_000266.2	Q04671-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
OCA2	ENST00000354638.8 link	c.228-14869A>G	intron_variant	Intron 2 of 23	1	NM_000275.3	ENSP00000346659.3	Q04671-1
OCA2	ENST00000353809.9 link	c.228-14869A>G	intron_variant	Intron 2 of 22	1		ENSP00000261276.8	Q04671-2
OCA2	ENST00000431101.1 link	c.228-14869A>G	intron_variant	Intron 2 of 6	3		ENSP00000415431.1	C9JDV3
OCA2	ENST00000445578.5 link	c.228-14869A>G	intron_variant	Intron 2 of 5	3		ENSP00000414425.1	C9JLG9

Frequencies

GnomAD3 genomes

AF:

0.286

AC:

43435

AN:

151872

Hom.:

8993

Cov.:

show subpopulations

Gnomad AFR

AF:

0.489

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.879

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.302

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

GnomAD4 genome

AF:

0.286

AC:

43513

AN:

151992

Hom.:

9018

Cov.:

AF XY:

0.295

AC XY:

21927

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.489

AC:

20276

AN:

41438

American (AMR)

AF:

0.304

AC:

4646

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

699

AN:

3472

East Asian (EAS)

AF:

0.879

AC:

4518

AN:

5140

South Asian (SAS)

AF:

0.384

AC:

1844

AN:

4802

European-Finnish (FIN)

AF:

0.151

AC:

1604

AN:

10596

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.133

AC:

9030

AN:

67958

Other (OTH)

AF:

0.309

AC:

652

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1304

2608

3912

5216

6520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<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:

0.149

Hom.:

470

Bravo

AF:

0.305

Asia WGS

AF:

0.587

AC:

2037

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.69

(source)

DANN

Benign

0.67

PhyloP100

-0.71

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over