15-28028204-T-C

Variant names:

• chr15-28028204-T-C
• rs2290100
• NM_000275.3:c.327-145A>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.327-145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 933,662 control chromosomes in the GnomAD database, including 9,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (1344 hom., cov: 33)
  • Exomes 𝑓: 0.063 (8230 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.182
• Publications: 2 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 15-28028204-T-C is Benign according to our data. Variant chr15-28028204-T-C is described in ClinVar as Benign. ClinVar VariationId is 1228242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.327-145A>G		intron_variant	Intron 3 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.327-145A>G		intron_variant	Intron 3 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.327-145A>G		intron_variant	Intron 3 of 22	1		ENSP00000261276.8
OCA2	ENST00000431101.1	c.327-145A>G		intron_variant	Intron 3 of 6	3		ENSP00000415431.1
OCA2	ENST00000445578.5	c.327-145A>G		intron_variant	Intron 3 of 5	3		ENSP00000414425.1

Frequencies

GnomAD3 genomes AF: 0.0658 AC: 10010 AN: 152190 Hom.: 1345 Cov.: 33

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0274

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0659

GnomAD4 exome AF: 0.0634 AC: 49518 AN: 781354 Hom.: 8230 AF XY: 0.0648 AC XY: 26472 AN XY: 408542

African (AFR) AF: 0.0605 AC: 1194 AN: 19724

American (AMR) AF: 0.0402 AC: 1407 AN: 35040

Ashkenazi Jewish (ASJ) AF: 0.0622 AC: 1328 AN: 21348

East Asian (EAS) AF: 0.653 AC: 21613 AN: 33106

South Asian (SAS) AF: 0.110 AC: 7394 AN: 66938

European-Finnish (FIN) AF: 0.0255 AC: 981 AN: 38462

Middle Eastern (MID) AF: 0.0493 AC: 159 AN: 3222

European-Non Finnish (NFE) AF: 0.0243 AC: 12787 AN: 525604

Other (OTH) AF: 0.0700 AC: 2655 AN: 37910

GnomAD4 genome AF: 0.0656 AC: 9998 AN: 152308 Hom.: 1344 Cov.: 33 AF XY: 0.0706 AC XY: 5255 AN XY: 74476

African (AFR) AF: 0.0650 AC: 2701 AN: 41572

American (AMR) AF: 0.0505 AC: 772 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 247 AN: 3468

East Asian (EAS) AF: 0.660 AC: 3412 AN: 5166

South Asian (SAS) AF: 0.136 AC: 657 AN: 4826

European-Finnish (FIN) AF: 0.0274 AC: 291 AN: 10626

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0255 AC: 1733 AN: 68028

Other (OTH) AF: 0.0657 AC: 139 AN: 2116

Alfa AF: 0.0467 Hom.: 1549

Bravo AF: 0.0684

Asia WGS AF: 0.292 AC: 1014 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.42
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2290100; hg19: chr15-28273350;