15-27871190-C-T

Variant names:

• chr15-27871190-C-T
• rs1800418
• NM_000275.3:c.2208G>A

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.2208G>A​(p.Ser736Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 1,613,988 control chromosomes in the GnomAD database, including 123 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. S736S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.016 (60 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (63 hom.)
• Consequence: OCA2 NM_000275.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -7.27
• 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: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-27871190-C-T is Benign according to our data. Variant chr15-27871190-C-T is described in ClinVar as Benign. ClinVar VariationId is 255729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-7.27 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0527 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.2208G>A	p.Ser736Ser	synonymous	Exon 21 of 24	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.2136G>A	p.Ser712Ser	synonymous	Exon 20 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.2208G>A	p.Ser736Ser	synonymous	Exon 21 of 24	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.2136G>A	p.Ser712Ser	synonymous	Exon 20 of 23	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.2412G>A	p.Ser804Ser	synonymous	Exon 22 of 26	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2421 AN: 152050 Hom.: 57 Cov.: 33

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00734

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.0144

GnomAD2 exomes AF: 0.00506 AC: 1272 AN: 251366 AF XY: 0.00391

Gnomad AFR exome AF: 0.0509

Gnomad AMR exome AF: 0.00353

Gnomad ASJ exome AF: 0.0162

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000985

Gnomad OTH exome AF: 0.00717

GnomAD4 exome AF: 0.00261 AC: 3816 AN: 1461820 Hom.: 63 Cov.: 32 AF XY: 0.00237 AC XY: 1723 AN XY: 727226

African (AFR) AF: 0.0548 AC: 1834 AN: 33458

American (AMR) AF: 0.00467 AC: 209 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0166 AC: 435 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5768

European-Non Finnish (NFE) AF: 0.000801 AC: 891 AN: 1111974

Other (OTH) AF: 0.00644 AC: 389 AN: 60392

GnomAD4 genome AF: 0.0161 AC: 2449 AN: 152168 Hom.: 60 Cov.: 33 AF XY: 0.0153 AC XY: 1135 AN XY: 74382

African (AFR) AF: 0.0518 AC: 2149 AN: 41506

American (AMR) AF: 0.00733 AC: 112 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00118 AC: 80 AN: 68002

Other (OTH) AF: 0.0142 AC: 30 AN: 2110

Alfa AF: 0.00608 Hom.: 9

Bravo AF: 0.0191

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	Tyrosinase-positive oculocutaneous albinism (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0050
DANN	Benign	0.57
PhyloP100		-7.3
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: rs1800418; hg19: chr15-28116336;