rs41534647

Variant names:

• chr15-28022612-A-G
• rs41534647
• NM_000275.3:c.574-39T>C

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.574-39T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,439,114 control chromosomes in the GnomAD database, including 347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (161 hom., cov: 33)
  • Exomes 𝑓: 0.010 (186 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.621
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-28022612-A-G is Benign according to our data. Variant chr15-28022612-A-G is described in ClinVar as Benign. ClinVar VariationId is 1224639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.082 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.574-39T>C		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.574-39T>C		intron	N/A	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.574-39T>C		intron	N/A	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.574-39T>C		intron	N/A	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.574-39T>C		intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.0300 AC: 4573 AN: 152204 Hom.: 160 Cov.: 33

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00982

Gnomad OTH AF: 0.0278

GnomAD2 exomes AF: 0.0123 AC: 3077 AN: 249624 AF XY: 0.0109

Gnomad AFR exome AF: 0.0863

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.00380

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.000750

Gnomad NFE exome AF: 0.00957

Gnomad OTH exome AF: 0.0133

GnomAD4 exome AF: 0.0103 AC: 13305 AN: 1286790 Hom.: 186 Cov.: 20 AF XY: 0.00985 AC XY: 6400 AN XY: 649640

African (AFR) AF: 0.0916 AC: 2768 AN: 30232

American (AMR) AF: 0.0124 AC: 552 AN: 44442

Ashkenazi Jewish (ASJ) AF: 0.00320 AC: 80 AN: 24976

East Asian (EAS) AF: 0.00 AC: 0 AN: 38882

South Asian (SAS) AF: 0.00303 AC: 250 AN: 82562

European-Finnish (FIN) AF: 0.00106 AC: 56 AN: 52964

Middle Eastern (MID) AF: 0.0184 AC: 100 AN: 5434

European-Non Finnish (NFE) AF: 0.00919 AC: 8751 AN: 952580

Other (OTH) AF: 0.0137 AC: 748 AN: 54718

GnomAD4 genome AF: 0.0301 AC: 4585 AN: 152324 Hom.: 161 Cov.: 33 AF XY: 0.0289 AC XY: 2154 AN XY: 74490

African (AFR) AF: 0.0843 AC: 3505 AN: 41566

American (AMR) AF: 0.0197 AC: 302 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4832

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10624

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00982 AC: 668 AN: 68038

Other (OTH) AF: 0.0275 AC: 58 AN: 2112

Alfa AF: 0.0222 Hom.: 39

Bravo AF: 0.0344

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.88
DANN	Benign	0.54
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs41534647; hg19: chr15-28267758;