Genetic Variant OCA2:c.1364+26A>G (chr15-27985038-T-C) – 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.1364+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,612,654 control chromosomes in the GnomAD database, including 37,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 5112 hom., cov: 33)

Exomes 𝑓: 0.16 ( 32294 hom. )

Consequence

OCA2
NM_000275.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.80

Publications

12 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 15-27985038-T-C is Benign according to our data. Variant chr15-27985038-T-C is described in ClinVar as Benign. ClinVar VariationId is 1273632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3 link	c.1364+26A>G		intron_variant	Intron 13 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8 link	c.1364+26A>G		intron_variant	Intron 13 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9 link	c.1292+26A>G		intron_variant	Intron 12 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32386

AN:

151976

Hom.:

5109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.289

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.848

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.219

GnomAD2 exomes

AF:

0.237

AC:

58637

AN:

247242

AF XY:

0.229

show subpopulations

Gnomad AFR exome

AF:

0.290

Gnomad AMR exome

AF:

0.348

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.848

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.196

GnomAD4 exome

AF:

0.160

AC:

234024

AN:

1460560

Hom.:

32294

Cov.:

AF XY:

0.162

AC XY:

117472

AN XY:

726572

show subpopulations

African (AFR)

AF:

0.289

AC:

9670

AN:

33450

American (AMR)

AF:

0.338

AC:

15024

AN:

44504

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

5481

AN:

26128

East Asian (EAS)

AF:

0.880

AC:

34879

AN:

39614

South Asian (SAS)

AF:

0.247

AC:

21314

AN:

86160

European-Finnish (FIN)

AF:

0.128

AC:

6786

AN:

53166

Middle Eastern (MID)

AF:

0.185

AC:

1065

AN:

5758

European-Non Finnish (NFE)

AF:

0.116

AC:

128644

AN:

1111428

Other (OTH)

AF:

0.185

AC:

11161

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

9698

19396

29093

38791

48489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5188

10376

15564

20752

25940

<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:

0.213

AC:

32434

AN:

152094

Hom.:

5112

Cov.:

AF XY:

0.219

AC XY:

16300

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.290

AC:

12021

AN:

41492

American (AMR)

AF:

0.270

AC:

4126

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

694

AN:

3470

East Asian (EAS)

AF:

0.848

AC:

4355

AN:

5134

South Asian (SAS)

AF:

0.265

AC:

1274

AN:

4814

European-Finnish (FIN)

AF:

0.128

AC:

1359

AN:

10590

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7982

AN:

67990

Other (OTH)

AF:

0.219

AC:

461

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1187

2375

3562

4750

5937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.156

Hom.:

1958

Bravo

AF:

0.230

Asia WGS

AF:

0.482

AC:

1670

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.046

(source)

DANN

Benign

0.31

PhyloP100

-2.8

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over