Genetic Variant OCA2:c.228-11240C>T (chr15-28043403-G-A) – 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.228-11240C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,112 control chromosomes in the GnomAD database, including 21,309 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 0.44 ( 21309 hom., cov: 32)

Consequence

OCA2
NM_000275.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.337

Publications

4 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:

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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=-1.01).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3 link	c.228-11240C>T		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.228-11240C>T	intron_variant	Intron 2 of 23	1	NM_000275.3	ENSP00000346659.3	Q04671-1
OCA2	ENST00000353809.9 link	c.228-11240C>T	intron_variant	Intron 2 of 22	1		ENSP00000261276.8	Q04671-2
OCA2	ENST00000431101.1 link	c.228-11240C>T	intron_variant	Intron 2 of 6	3		ENSP00000415431.1	C9JDV3
OCA2	ENST00000445578.5 link	c.228-11240C>T	intron_variant	Intron 2 of 5	3		ENSP00000414425.1	C9JLG9

Frequencies

GnomAD3 genomes

AF:

0.443

AC:

67321

AN:

151994

Hom.:

21253

Cov.:

show subpopulations

Gnomad AFR

AF:

0.855

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.363

Gnomad EAS

AF:

0.893

Gnomad SAS

AF:

0.445

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.444

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

GnomAD4 genome

AF:

0.443

AC:

67437

AN:

152112

Hom.:

21309

Cov.:

AF XY:

0.446

AC XY:

33145

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.855

AC:

35494

AN:

41490

American (AMR)

AF:

0.402

AC:

6138

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.363

AC:

1261

AN:

3472

East Asian (EAS)

AF:

0.893

AC:

4610

AN:

5162

South Asian (SAS)

AF:

0.444

AC:

2135

AN:

4806

European-Finnish (FIN)

AF:

0.176

AC:

1870

AN:

10600

Middle Eastern (MID)

AF:

0.503

AC:

147

AN:

292

European-Non Finnish (NFE)

AF:

0.216

AC:

14673

AN:

67996

Other (OTH)

AF:

0.450

AC:

948

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1284

2568

3853

5137

6421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

540

1080

1620

2160

2700

<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:

0.357

Hom.:

6002

Bravo

AF:

0.480

Asia WGS

AF:

0.656

AC:

2277

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.49

(source)

DANN

Benign

0.67

PhyloP100

-0.34

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