15-27926148-T-G

Variant names:

• chr15-27926148-T-G
• rs1800416
• NM_000275.3:c.2058A>C
• OCA2 p.Ala686Ala

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000275.3(OCA2):​c.2058A>C​(p.Ala686Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,614,022 control chromosomes in the GnomAD database, including 1,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A686A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.053 (746 hom., cov: 33)
  • Exomes 𝑓: 0.0059 (693 hom.)
• Consequence: OCA2 NM_000275.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.868
• Publications: 3 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: G2P, ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 15-27926148-T-G is Benign according to our data. Variant chr15-27926148-T-G is described in ClinVar as Benign. ClinVar VariationId is 255727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.868 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.2058A>C	p.Ala686Ala	synonymous	Exon 19 of 24	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.1986A>C	p.Ala662Ala	synonymous	Exon 18 of 23	NP_001287913.1	Q04671-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.2058A>C	p.Ala686Ala	synonymous	Exon 19 of 24	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.1986A>C	p.Ala662Ala	synonymous	Exon 18 of 23	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.2058A>C	p.Ala686Ala	synonymous	Exon 19 of 26	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8125 AN: 152114 Hom.: 745 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.0378

GnomAD2 exomes AF: 0.0145 AC: 3634 AN: 251184 AF XY: 0.0106

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.00784

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.00799

GnomAD4 exome AF: 0.00593 AC: 8663 AN: 1461790 Hom.: 693 Cov.: 32 AF XY: 0.00520 AC XY: 3782 AN XY: 727196

African (AFR) AF: 0.196 AC: 6548 AN: 33474

American (AMR) AF: 0.00903 AC: 404 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00122 AC: 32 AN: 26130

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39676

South Asian (SAS) AF: 0.00118 AC: 102 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.00971 AC: 56 AN: 5766

European-Non Finnish (NFE) AF: 0.000662 AC: 736 AN: 1111958

Other (OTH) AF: 0.0129 AC: 781 AN: 60388

GnomAD4 genome AF: 0.0535 AC: 8142 AN: 152232 Hom.: 746 Cov.: 33 AF XY: 0.0514 AC XY: 3823 AN XY: 74442

African (AFR) AF: 0.186 AC: 7727 AN: 41510

American (AMR) AF: 0.0159 AC: 243 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00121 AC: 82 AN: 68008

Other (OTH) AF: 0.0374 AC: 79 AN: 2114

Alfa AF: 0.0201 Hom.: 178

Bravo AF: 0.0606

EpiCase AF: 0.00174

EpiControl AF: 0.00184

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Tyrosinase-positive oculocutaneous albinism (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.68
DANN	Benign	0.48
PhyloP100		-0.87
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1800416;

hg19: chr15-28171294;