rs374819923

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_StrongBP6_Very_StrongBP7BS1BS2_Supporting

The NM_000275.3(OCA2):c.144G>A(p.Ser48Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000301 in 1,613,566 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00031 ( 5 hom. )

Consequence

OCA2
NM_000275.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.31

Publications

1 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 15-28081731-C-T is Benign according to our data. Variant chr15-28081731-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 255721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-28081731-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 255721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-28081731-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 255721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-28081731-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 255721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-28081731-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 255721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-28081731-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 255721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-28081731-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 255721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-28081731-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 255721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-28081731-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 255721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-28081731-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 255721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-28081731-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 255721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-28081731-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 255721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.31 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000305 (446/1461242) while in subpopulation AMR AF = 0.00872 (390/44704). AF 95% confidence interval is 0.00801. There are 5 homozygotes in GnomAdExome4. There are 195 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 5 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3 link	c.144G>A	p.Ser48Ser	synonymous_variant	Exon 2 of 24	ENST00000354638.8	NP_000266.2	Q04671-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OCA2	ENST00000354638.8 link	c.144G>A	p.Ser48Ser	synonymous_variant	Exon 2 of 24	1	NM_000275.3	ENSP00000346659.3	Q04671-1
OCA2	ENST00000353809.9 link	c.144G>A	p.Ser48Ser	synonymous_variant	Exon 2 of 23	1		ENSP00000261276.8	Q04671-2
OCA2	ENST00000431101.1 link	c.144G>A	p.Ser48Ser	synonymous_variant	Exon 2 of 7	3		ENSP00000415431.1	C9JDV3
OCA2	ENST00000445578.5 link	c.144G>A	p.Ser48Ser	synonymous_variant	Exon 2 of 6	3		ENSP00000414425.1	C9JLG9

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00153

AC:

377

AN:

245922

AF XY:

0.00120

show subpopulations

Gnomad AFR exome

AF:

0.000256

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000547

Gnomad OTH exome

AF:

0.000829

GnomAD4 exome

AF:

0.000305

AC:

446

AN:

1461242

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

195

AN XY:

726898

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33476

American (AMR)

AF:

0.00872

AC:

390

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000369

AC:

AN:

1111878

Other (OTH)

AF:

0.000133

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

126

158

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:

0.000256

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41578

American (AMR)

AF:

0.00176

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.000706

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Tyrosinase-positive oculocutaneous albinism

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided

Benign:1

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.45

(source)

DANN

Benign

0.57

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism

(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