chr15-27957427-G-A

Variant names:

• chr15-27957427-G-A
• rs11638265
• NM_000275.3:c.1784+161C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000275.3(OCA2):​c.1784+161C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,044 control chromosomes in the GnomAD database, including 24,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.51 (24351 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.250
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-27957427-G-A is Benign according to our data. Variant chr15-27957427-G-A is described in ClinVar as Benign. ClinVar VariationId is 1277786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000275.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.1784+161C>T		intron	N/A	NP_000266.2
	OCA2	NM_001300984.2		c.1712+161C>T		intron	N/A	NP_001287913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.1784+161C>T		intron	N/A	ENSP00000346659.3
	OCA2	ENST00000353809.9	TSL:1	c.1712+161C>T		intron	N/A	ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77381 AN: 151926 Hom.: 24360 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.509 AC: 77364 AN: 152044 Hom.: 24351 Cov.: 32 AF XY: 0.503 AC XY: 37363 AN XY: 74308

African (AFR) AF: 0.186 AC: 7718 AN: 41460

American (AMR) AF: 0.425 AC: 6494 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2061 AN: 3472

East Asian (EAS) AF: 0.150 AC: 773 AN: 5156

South Asian (SAS) AF: 0.321 AC: 1545 AN: 4816

European-Finnish (FIN) AF: 0.746 AC: 7882 AN: 10564

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48951 AN: 67988

Other (OTH) AF: 0.513 AC: 1079 AN: 2104

Alfa AF: 0.625 Hom.: 46440

Bravo AF: 0.475

Asia WGS AF: 0.287 AC: 999 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.84
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11638265; hg19: chr15-28202573; COSMIC: COSV62350847;