rs41534647

chr15-28022612-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000275.3(OCA2):c.574-39T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,439,114 control chromosomes in the GnomAD database, including 347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (161 hom., cov: 33)
  • Exomes 𝑓: 0.010 (186 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.621

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-28022612-A-G is Benign according to our data. Variant chr15-28022612-A-G is described in ClinVar as [Benign]. Clinvar id is 1224639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.082 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.574-39T>C		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.574-39T>C		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.574-39T>C		intron_variant		1
OCA2	ENST00000431101.1	c.574-39T>C		intron_variant		3
OCA2	ENST00000445578.5	c.573+2233T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0300 AC: 4573 AN: 152204 Hom.: 160 Cov.: 33

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00982

Gnomad OTH AF: 0.0278

GnomAD3 exomes AF: 0.0123 AC: 3077 AN: 249624 Hom.: 70 AF XY: 0.0109 AC XY: 1475 AN XY: 135040

Gnomad AFR exome AF: 0.0863

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.00380

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00279

Gnomad FIN exome AF: 0.000750

Gnomad NFE exome AF: 0.00957

Gnomad OTH exome AF: 0.0133

GnomAD4 exome AF: 0.0103 AC: 13305 AN: 1286790 Hom.: 186 Cov.: 20 AF XY: 0.00985 AC XY: 6400 AN XY: 649640

Gnomad4 AFR exome AF: 0.0916

Gnomad4 AMR exome AF: 0.0124

Gnomad4 ASJ exome AF: 0.00320

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00303

Gnomad4 FIN exome AF: 0.00106

Gnomad4 NFE exome AF: 0.00919

Gnomad4 OTH exome AF: 0.0137

GnomAD4 genome AF: 0.0301 AC: 4585 AN: 152324 Hom.: 161 Cov.: 33 AF XY: 0.0289 AC XY: 2154 AN XY: 74490

Gnomad4 AFR AF: 0.0843

Gnomad4 AMR AF: 0.0197

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00982

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0250 Hom.: 24

Bravo AF: 0.0344

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.88
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs41534647; hg19: chr15-28267758;