rs2290100

Variant names:

• chr15-28028204-T-A
• rs2290100
• NM_000275.3:c.327-145A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-28028204-T-A
• chr15-28028204-T-C
• chr15-28028204-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000275.3(OCA2):​c.327-145A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 781492 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 408616

African (AFR) AF: 0.00 AC: 0 AN: 19726

American (AMR) AF: 0.00 AC: 0 AN: 35042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21348

East Asian (EAS) AF: 0.00 AC: 0 AN: 33122

South Asian (SAS) AF: 0.00 AC: 0 AN: 66950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3224

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 525698

Other (OTH) AF: 0.00 AC: 0 AN: 37918

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.47
PhyloP100		0.18

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: rs2290100; hg19: chr15-28273350;