Genetic Variant OCA2:c.2433-21343A>C (chr15-27776815-T-G) – 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.2433-21343A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,238 control chromosomes in the GnomAD database, including 2,302 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 0.14 ( 2302 hom., cov: 31)

Exomes 𝑓: 0.032 ( 0 hom. )

Consequence

OCA2
NM_000275.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0150

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

OCA2 links:

ENSG00000232394 (HGNC:):

ENSG00000232394 links:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3 link	c.2433-21343A>C		intron_variant	Intron 23 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.2433-21343A>C	intron_variant	Intron 23 of 23	1	NM_000275.3	ENSP00000346659.3	Q04671-1
OCA2	ENST00000353809.9 link	c.2361-21343A>C	intron_variant	Intron 22 of 22	1		ENSP00000261276.8	Q04671-2
ENSG00000232394	ENST00000419100.1 link	n.*17T>G	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20658

AN:

151966

Hom.:

2301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.0712

Gnomad EAS

AF:

0.586

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0598

Gnomad OTH

AF:

0.122

GnomAD4 exome

AF:

0.0325

AC:

AN:

154

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

AN XY:

112

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0403

AC:

AN:

124

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.136

AC:

20674

AN:

152084

Hom.:

2302

Cov.:

AF XY:

0.143

AC XY:

10611

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.215

AC:

8922

AN:

41470

American (AMR)

AF:

0.123

AC:

1881

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0712

AC:

247

AN:

3470

East Asian (EAS)

AF:

0.586

AC:

2998

AN:

5118

South Asian (SAS)

AF:

0.124

AC:

594

AN:

4808

European-Finnish (FIN)

AF:

0.156

AC:

1650

AN:

10596

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0598

AC:

4066

AN:

68020

Other (OTH)

AF:

0.123

AC:

260

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

822

1644

2465

3287

4109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<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:

0.0447

Hom.:

Bravo

AF:

0.143

Asia WGS

AF:

0.309

AC:

1074

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.3

(source)

DANN

Benign

0.74

PhyloP100

0.015

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