Genetic Variant NM_000275.3:c.1239+376C>A (chr15-27986211-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000275.3(OCA2):c.1239+376C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,090 control chromosomes in the GnomAD database, including 41,436 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 0.72 ( 41436 hom., cov: 32)

Consequence

OCA2
NM_000275.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.988

Publications

4 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: Ambry Genetics, ClinGen, G2P, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
oculocutaneous albinism
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

OCA2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000275.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.1239+376C>A		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.1167+376C>A		intron	N/A	NP_001287913.1	Q04671-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OCA2	ENST00000354638.8	TSL:1 MANE Select	c.1239+376C>A	intron	N/A	ENSP00000346659.3	Q04671-1
OCA2	ENST00000353809.9	TSL:1	c.1167+376C>A	intron	N/A	ENSP00000261276.8	Q04671-2
OCA2	ENST00000910120.1		c.1239+376C>A	intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes

AF:

0.720

AC:

109365

AN:

151972

Hom.:

41439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.873

Gnomad AMR

AF:

0.700

Gnomad ASJ

AF:

0.813

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.615

Gnomad FIN

AF:

0.871

Gnomad MID

AF:

0.788

Gnomad NFE

AF:

0.829

Gnomad OTH

AF:

0.734

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

GnomAD4 genome

AF:

0.719

AC:

109384

AN:

152090

Hom.:

41436

Cov.:

AF XY:

0.720

AC XY:

53542

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.472

AC:

19549

AN:

41434

American (AMR)

AF:

0.699

AC:

10683

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.813

AC:

2821

AN:

3470

East Asian (EAS)

AF:

0.998

AC:

5175

AN:

5186

South Asian (SAS)

AF:

0.615

AC:

2956

AN:

4808

European-Finnish (FIN)

AF:

0.871

AC:

9221

AN:

10584

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.829

AC:

56408

AN:

68008

Other (OTH)

AF:

0.732

AC:

1545

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1406

2811

4217

5622

7028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

822

1644

2466

3288

4110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.756

Hom.:

21387

Bravo

AF:

0.702

Asia WGS

AF:

0.787

AC:

2735

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.17

(source)

DANN

Benign

0.18

PhyloP100

-0.99

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over