rs12439067

Variant names:

• chr15-27957479-C-A
• rs12439067
• NM_000275.3:c.1784+109G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-27957479-C-A
• chr15-27957479-C-G
• chr15-27957479-C-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+109G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,290,454 control chromosomes in the GnomAD database, including 21,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2809 hom., cov: 33)
  • Exomes 𝑓: 0.10 (19019 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.01
• Publications: 2 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=-0.87).
• BP6: Variant 15-27957479-C-A is Benign according to our data. Variant chr15-27957479-C-A is described in ClinVar as Benign. ClinVar VariationId is 1263331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.1784+109G>T		intron_variant	Intron 16 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.1784+109G>T		intron_variant	Intron 16 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.1712+109G>T		intron_variant	Intron 15 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19331 AN: 152046 Hom.: 2814 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0580

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.100 AC: 113900 AN: 1138290 Hom.: 19019 AF XY: 0.0989 AC XY: 57147 AN XY: 577792

African (AFR) AF: 0.154 AC: 4212 AN: 27380

American (AMR) AF: 0.239 AC: 10513 AN: 43978

Ashkenazi Jewish (ASJ) AF: 0.0581 AC: 1374 AN: 23660

East Asian (EAS) AF: 0.875 AC: 33082 AN: 37818

South Asian (SAS) AF: 0.112 AC: 8798 AN: 78654

European-Finnish (FIN) AF: 0.0954 AC: 4375 AN: 45848

Middle Eastern (MID) AF: 0.0651 AC: 232 AN: 3564

European-Non Finnish (NFE) AF: 0.0555 AC: 45956 AN: 827848

Other (OTH) AF: 0.108 AC: 5358 AN: 49540

GnomAD4 genome AF: 0.127 AC: 19341 AN: 152164 Hom.: 2809 Cov.: 33 AF XY: 0.132 AC XY: 9828 AN XY: 74384

African (AFR) AF: 0.155 AC: 6453 AN: 41502

American (AMR) AF: 0.159 AC: 2425 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0580 AC: 201 AN: 3468

East Asian (EAS) AF: 0.836 AC: 4307 AN: 5154

South Asian (SAS) AF: 0.128 AC: 619 AN: 4818

European-Finnish (FIN) AF: 0.101 AC: 1068 AN: 10604

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0586 AC: 3985 AN: 68012

Other (OTH) AF: 0.125 AC: 264 AN: 2106

Alfa AF: 0.0319 Hom.: 28

Bravo AF: 0.138

Asia WGS AF: 0.399 AC: 1385 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.87
CADD	Benign	0.020
DANN	Benign	0.53
PhyloP100		-1.0
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: rs12439067; hg19: chr15-28202625;