Genetic Variant NM_000275.3:c.79G>C (chr15-28081796-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000275.3(OCA2):c.79G>C(p.Gly27Arg) variant causes a missense 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

OCA2
NM_000275.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.128

Publications

5 publications found

Variant links:

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

OCA2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16696575).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000275.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.79G>C	p.Gly27Arg	missense	Exon 2 of 24	NP_000266.2
	OCA2	NM_001300984.2		c.79G>C	p.Gly27Arg	missense	Exon 2 of 23	NP_001287913.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OCA2	ENST00000354638.8	TSL:1 MANE Select	c.79G>C	p.Gly27Arg	missense	Exon 2 of 24	ENSP00000346659.3
OCA2	ENST00000353809.9	TSL:1	c.79G>C	p.Gly27Arg	missense	Exon 2 of 23	ENSP00000261276.8
OCA2	ENST00000431101.1	TSL:3	c.79G>C	p.Gly27Arg	missense	Exon 2 of 7	ENSP00000415431.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000412

AC:

AN:

242598

AF XY:

0.00000752

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000924

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000826

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

CADD

Benign

3.7

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.28

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.61

M_CAP

Benign

0.024

MetaRNN

Benign

0.17

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

0.90

PhyloP100

0.13

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.54

REVEL

Uncertain

0.35

Sift

Benign

0.80

Sift4G

Benign

0.66

Polyphen

0.0010

Vest4

0.59

MutPred

0.65

Gain of MoRF binding (P = 0.0199)

MVP

0.73

MPC

0.11

ClinPred

0.045

GERP RS

-6.2

Varity_R

0.047

gMVP

0.19

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over