NM_000275.3:c.-22+7161T>C

Variant names:

• chr15-28092063-A-G
• rs73377792
• NM_000275.3:c.-22+7161T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000275.3(OCA2):​c.-22+7161T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 152,304 control chromosomes in the GnomAD database, including 460 homozygotes. 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: 𝑓 0.063 (460 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.-22+7161T>C		intron_variant	Intron 1 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.-22+7161T>C		intron_variant	Intron 1 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.-22+7161T>C		intron_variant	Intron 1 of 22	1		ENSP00000261276.8
OCA2	ENST00000431101.1	c.-22+7048T>C		intron_variant	Intron 1 of 6	3		ENSP00000415431.1
OCA2	ENST00000445578.5	c.-22+7161T>C		intron_variant	Intron 1 of 5	3		ENSP00000414425.1

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9513 AN: 152186 Hom.: 456 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.0811

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0349

Gnomad OTH AF: 0.0750

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0626 AC: 9538 AN: 152304 Hom.: 460 Cov.: 33 AF XY: 0.0626 AC XY: 4664 AN XY: 74472

African (AFR) AF: 0.131 AC: 5462 AN: 41544

American (AMR) AF: 0.0581 AC: 888 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3470

East Asian (EAS) AF: 0.0164 AC: 85 AN: 5188

South Asian (SAS) AF: 0.0810 AC: 391 AN: 4830

European-Finnish (FIN) AF: 0.00301 AC: 32 AN: 10624

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0349 AC: 2374 AN: 68034

Other (OTH) AF: 0.0733 AC: 155 AN: 2116

Alfa AF: 0.0576 Hom.: 74

Bravo AF: 0.0694

Asia WGS AF: 0.0500 AC: 173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		0.14
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: rs73377792; hg19: chr15-28337209;