dbSNP rs11631195: OCA2:c.2433-21270C>T (chr15-27776742-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.2433-21270C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,176 control chromosomes in the GnomAD database, including 6,819 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 0.27 ( 6806 hom., cov: 31)

Exomes 𝑓: 0.37 ( 13 hom. )

Consequence

OCA2
NM_000275.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

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

OCA2 links:

ENSG00000232394 (HGNC:):

ENSG00000232394 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=-0.94).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 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.2433-21270C>T		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.2361-21270C>T		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.2433-21270C>T	intron	N/A	ENSP00000346659.3	Q04671-1
OCA2	ENST00000353809.9	TSL:1	c.2361-21270C>T	intron	N/A	ENSP00000261276.8	Q04671-2
OCA2	ENST00000910120.1		c.2679-21270C>T	intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41607

AN:

151892

Hom.:

6803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.368

Gnomad OTH

AF:

0.226

GnomAD4 exome

AF:

0.367

AC:

AN:

166

Hom.:

Cov.:

AF XY:

0.347

AC XY:

AN XY:

124

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.417

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.396

AC:

AN:

134

Other (OTH)

AF:

0.375

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.274

AC:

41627

AN:

152010

Hom.:

6806

Cov.:

AF XY:

0.267

AC XY:

19858

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.166

AC:

6905

AN:

41484

American (AMR)

AF:

0.206

AC:

3146

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

871

AN:

3472

East Asian (EAS)

AF:

0.00117

AC:

AN:

5150

South Asian (SAS)

AF:

0.107

AC:

515

AN:

4810

European-Finnish (FIN)

AF:

0.418

AC:

4413

AN:

10564

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.368

AC:

25024

AN:

67922

Other (OTH)

AF:

0.223

AC:

471

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1417

2834

4252

5669

7086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.322

Hom.:

14235

Bravo

AF:

0.256

Asia WGS

AF:

0.0620

AC:

214

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.64

(source)

DANN

Benign

0.61

PhyloP100

-1.0

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