NM_000275.3:c.1785-47A>G

Variant names:

• chr15-27955262-T-C
• rs7170989
• NM_000275.3:c.1785-47A>G

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.1785-47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 1,386,276 control chromosomes in the GnomAD database, including 357,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (30680 hom., cov: 34)
  • Exomes 𝑓: 0.71 (326424 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.147
• Publications: 12 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=-0.93).
• BP6: Variant 15-27955262-T-C is Benign according to our data. Variant chr15-27955262-T-C is described in ClinVar as Benign. ClinVar VariationId is 1252195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.1785-47A>G		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.1785-47A>G		intron_variant	Intron 16 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.1713-47A>G		intron_variant	Intron 15 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91540 AN: 152086 Hom.: 30686 Cov.: 34

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.606

GnomAD2 exomes AF: 0.613 AC: 153774 AN: 250994 AF XY: 0.620

Gnomad AFR exome AF: 0.366

Gnomad AMR exome AF: 0.412

Gnomad ASJ exome AF: 0.741

Gnomad EAS exome AF: 0.141

Gnomad FIN exome AF: 0.761

Gnomad NFE exome AF: 0.779

Gnomad OTH exome AF: 0.668

GnomAD4 exome AF: 0.709 AC: 874359 AN: 1234072 Hom.: 326424 Cov.: 17 AF XY: 0.704 AC XY: 440477 AN XY: 626018

African (AFR) AF: 0.352 AC: 10200 AN: 28942

American (AMR) AF: 0.425 AC: 18864 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 18412 AN: 24772

East Asian (EAS) AF: 0.108 AC: 4167 AN: 38610

South Asian (SAS) AF: 0.490 AC: 40013 AN: 81582

European-Finnish (FIN) AF: 0.764 AC: 40558 AN: 53082

Middle Eastern (MID) AF: 0.703 AC: 3770 AN: 5360

European-Non Finnish (NFE) AF: 0.777 AC: 702797 AN: 904408

Other (OTH) AF: 0.673 AC: 35578 AN: 52878

GnomAD4 genome AF: 0.602 AC: 91563 AN: 152204 Hom.: 30680 Cov.: 34 AF XY: 0.596 AC XY: 44339 AN XY: 74418

African (AFR) AF: 0.370 AC: 15360 AN: 41504

American (AMR) AF: 0.501 AC: 7661 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2534 AN: 3470

East Asian (EAS) AF: 0.146 AC: 757 AN: 5180

South Asian (SAS) AF: 0.470 AC: 2266 AN: 4824

European-Finnish (FIN) AF: 0.753 AC: 7982 AN: 10598

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52731 AN: 68012

Other (OTH) AF: 0.602 AC: 1273 AN: 2116

Alfa AF: 0.669 Hom.: 10851

Bravo AF: 0.574

Asia WGS AF: 0.349 AC: 1216 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Tyrosinase-positive oculocutaneous albinism Benign:1

Sep 05, 2021

Genome-Nilou Lab

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	-0.93
CADD	Benign	2.5
DANN	Benign	0.33
PhyloP100		-0.15
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: rs7170989; hg19: chr15-28200408; COSMIC: COSV62341571;