15-27954896-C-T

Variant names:

• chr15-27954896-C-T
• rs728404
• NM_000275.3:c.1842+262G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000275.3(OCA2):​c.1842+262G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,200 control chromosomes in the GnomAD database, including 3,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (3480 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-27954896-C-T is Benign according to our data. Variant chr15-27954896-C-T is described in CliVar as Benign. Clinvar id is 1274710.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-27954896-C-T is described in CliVar as Benign. Clinvar id is 1274710.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-27954896-C-T is described in CliVar as Benign. Clinvar id is 1274710.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-27954896-C-T is described in CliVar as Benign. Clinvar id is 1274710.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-27954896-C-T is described in CliVar as Benign. Clinvar id is 1274710.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-27954896-C-T is described in CliVar as Benign. Clinvar id is 1274710.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-27954896-C-T is described in CliVar as Benign. Clinvar id is 1274710.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-27954896-C-T is described in CliVar as Benign. Clinvar id is 1274710.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-27954896-C-T is described in CliVar as Benign. Clinvar id is 1274710.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-27954896-C-T is described in CliVar as Benign. Clinvar id is 1274710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.1842+262G>A		intron_variant	Intron 17 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.1842+262G>A		intron_variant	Intron 17 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.1770+262G>A		intron_variant	Intron 16 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23056 AN: 152082 Hom.: 3486 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0677

Gnomad OTH AF: 0.153

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.152 AC: 23079 AN: 152200 Hom.: 3480 Cov.: 33 AF XY: 0.157 AC XY: 11712 AN XY: 74428

African (AFR) AF: 0.195 AC: 8116 AN: 41522

American (AMR) AF: 0.213 AC: 3256 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 448 AN: 3472

East Asian (EAS) AF: 0.857 AC: 4424 AN: 5160

South Asian (SAS) AF: 0.166 AC: 802 AN: 4828

European-Finnish (FIN) AF: 0.102 AC: 1083 AN: 10602

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0677 AC: 4602 AN: 67998

Other (OTH) AF: 0.154 AC: 325 AN: 2108

Alfa AF: 0.107 Hom.: 5540

Bravo AF: 0.168

Asia WGS AF: 0.451 AC: 1563 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

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	-0.86
CADD	Benign	0.73
DANN	Benign	0.51
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs728404; hg19: chr15-28200042;