Variant rs17566952 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000354638.8(OCA2):c.1951+45G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 1,346,208 control chromosomes in the GnomAD database, including 3,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 255 hom., cov: 33)

Exomes 𝑓: 0.064 ( 3114 hom. )

Consequence

OCA2
ENST00000354638.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.619

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 15-27951739-C-G is Benign according to our data. Variant chr15-27951739-C-G is described in ClinVar as [Benign]. Clinvar id is 1262515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCA2	NM_000275.3 linkuse as main transcript	c.1951+45G>C		intron_variant		ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8 linkuse as main transcript	c.1951+45G>C		intron_variant		1	NM_000275.3	ENSP00000346659	P1	Q04671-1
OCA2	ENST00000353809.9 linkuse as main transcript	c.1879+45G>C		intron_variant		1		ENSP00000261276		Q04671-2

Frequencies

GnomAD3 genomes

AF:

0.0479

AC:

7287

AN:

152176

Hom.:

254

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.0650

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.00751

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.0264

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0604

Gnomad OTH

AF:

0.0650

GnomAD3 exomes

AF:

0.0599

AC:

14348

AN:

239646

Hom.:

657

AF XY:

0.0661

AC XY:

8542

AN XY:

129178

show subpopulations

Gnomad AFR exome

AF:

0.00999

Gnomad AMR exome

AF:

0.0357

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.00626

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.0315

Gnomad NFE exome

AF:

0.0623

Gnomad OTH exome

AF:

0.0710

GnomAD4 exome

AF:

0.0637

AC:

76007

AN:

1193914

Hom.:

3114

Cov.:

AF XY:

0.0665

AC XY:

40363

AN XY:

606538

show subpopulations

Gnomad4 AFR exome

AF:

0.00903

Gnomad4 AMR exome

AF:

0.0380

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.00455

Gnomad4 SAS exome

AF:

0.129

Gnomad4 FIN exome

AF:

0.0308

Gnomad4 NFE exome

AF:

0.0623

Gnomad4 OTH exome

AF:

0.0675

GnomAD4 genome

AF:

0.0478

AC:

7284

AN:

152294

Hom.:

255

Cov.:

AF XY:

0.0491

AC XY:

3656

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.0649

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.00753

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.0264

Gnomad4 NFE

AF:

0.0604

Gnomad4 OTH

AF:

0.0643

Alfa

AF:

0.0440

Hom.:

Bravo

AF:

0.0466

Asia WGS

AF:

0.0500

AC:

172

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.37

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over