15-28022626-G-C

Position:

• chr15-28022626-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The ENST00000354638.8(OCA2):​c.574-53C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00828 in 1,354,468 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0086 (78 hom.)
• Consequence: OCA2 ENST00000354638.8 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High Homozygotes in GnomAd4 at 2 AD,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/exons	MANE	Protein	UniProt
OCA2	NM_000275.3	c.574-53C>G		intron_variant		ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.574-53C>G		intron_variant		1	NM_000275.3	ENSP00000346659	P1
OCA2	ENST00000353809.9	c.574-53C>G		intron_variant		1		ENSP00000261276
OCA2	ENST00000431101.1	c.574-53C>G		intron_variant		3		ENSP00000415431
OCA2	ENST00000445578.5	c.573+2219C>G		intron_variant		3		ENSP00000414425

Frequencies

GnomAD3 genomes AF: 0.00603 AC: 917 AN: 152178 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00413

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00992

Gnomad OTH AF: 0.00719

GnomAD4 exome AF: 0.00857 AC: 10297 AN: 1202172 Hom.: 78 AF XY: 0.00828 AC XY: 5056 AN XY: 610814

Gnomad4 AFR exome AF: 0.00256

Gnomad4 AMR exome AF: 0.00674

Gnomad4 ASJ exome AF: 0.00811

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00113

Gnomad4 FIN exome AF: 0.000766

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.00775

GnomAD4 genome AF: 0.00602 AC: 917 AN: 152296 Hom.: 2 Cov.: 33 AF XY: 0.00546 AC XY: 407 AN XY: 74480

Gnomad4 AFR AF: 0.00274

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00992

Gnomad4 OTH AF: 0.00712

Alfa AF: 0.00171 Hom.: 0

Bravo AF: 0.00635

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Tyrosinase-positive oculocutaneous albinism Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

MVZ Medizinische Genetik Mainz

Apr 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.53

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

LitVar

Other links and lift over

dbSNP: rs41276938; hg19: chr15-28267772;