15-27871129-G-C

Variant names:

• chr15-27871129-G-C
• rs7175046
• NM_000275.3:c.2244+25C>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.2244+25C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 1,569,672 control chromosomes in the GnomAD database, including 419,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (48096 hom., cov: 32)
  • Exomes 𝑓: 0.72 (371697 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.358
• Publications: 10 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=-0.91).
• BP6: Variant 15-27871129-G-C is Benign according to our data. Variant chr15-27871129-G-C is described in ClinVar as Benign. ClinVar VariationId is 1263011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2244+25C>G		intron_variant	Intron 21 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.2244+25C>G		intron_variant	Intron 21 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.2172+25C>G		intron_variant	Intron 20 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119468 AN: 152028 Hom.: 48033 Cov.: 32

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.898

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.839

GnomAD2 exomes AF: 0.781 AC: 195456 AN: 250336 AF XY: 0.780

Gnomad AFR exome AF: 0.928

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.852

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.663

Gnomad NFE exome AF: 0.687

Gnomad OTH exome AF: 0.780

GnomAD4 exome AF: 0.718 AC: 1017568 AN: 1417526 Hom.: 371697 Cov.: 24 AF XY: 0.723 AC XY: 511321 AN XY: 707690

African (AFR) AF: 0.934 AC: 30399 AN: 32548

American (AMR) AF: 0.852 AC: 38052 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 22063 AN: 25880

East Asian (EAS) AF: 0.999 AC: 39492 AN: 39514

South Asian (SAS) AF: 0.892 AC: 76206 AN: 85446

European-Finnish (FIN) AF: 0.657 AC: 35006 AN: 53306

Middle Eastern (MID) AF: 0.896 AC: 5121 AN: 5714

European-Non Finnish (NFE) AF: 0.678 AC: 726201 AN: 1071498

Other (OTH) AF: 0.764 AC: 45028 AN: 58962

GnomAD4 genome AF: 0.786 AC: 119591 AN: 152146 Hom.: 48096 Cov.: 32 AF XY: 0.790 AC XY: 58754 AN XY: 74372

African (AFR) AF: 0.927 AC: 38489 AN: 41534

American (AMR) AF: 0.822 AC: 12568 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 2950 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5152 AN: 5160

South Asian (SAS) AF: 0.893 AC: 4302 AN: 4820

European-Finnish (FIN) AF: 0.660 AC: 6992 AN: 10590

Middle Eastern (MID) AF: 0.894 AC: 261 AN: 292

European-Non Finnish (NFE) AF: 0.683 AC: 46403 AN: 67970

Other (OTH) AF: 0.840 AC: 1775 AN: 2112

Alfa AF: 0.700 Hom.: 4664

Bravo AF: 0.804

Asia WGS AF: 0.949 AC: 3302 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

Nov 12, 2018

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	-0.91
CADD	Benign	0.88
DANN	Benign	0.38
PhyloP100		-0.36
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: rs7175046; hg19: chr15-28116275;