Variant chr15-27957495-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000275.3(OCA2):c.1784+93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 1,409,974 control chromosomes in the GnomAD database, including 3,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 247 hom., cov: 33)

Exomes 𝑓: 0.061 ( 3039 hom. )

Consequence

OCA2
NM_000275.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0670

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 15-27957495-C-T is Benign according to our data. Variant chr15-27957495-C-T is described in ClinVar as [Benign]. Clinvar id is 1226185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCA2	NM_000275.3 link	c.1784+93G>A		intron_variant		ENST00000354638.8	NP_000266.2	Q04671-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8 link	c.1784+93G>A		intron_variant		1	NM_000275.3	ENSP00000346659.3		Q04671-1
OCA2	ENST00000353809.9 link	c.1712+93G>A		intron_variant		1		ENSP00000261276.8		Q04671-2

Frequencies

GnomAD3 genomes

AF:

0.0464

AC:

7060

AN:

152152

Hom.:

247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.0624

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.00771

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0271

Gnomad MID

AF:

0.0860

Gnomad NFE

AF:

0.0581

Gnomad OTH

AF:

0.0660

GnomAD4 exome

AF:

0.0615

AC:

77341

AN:

1257704

Hom.:

3039

AF XY:

0.0644

AC XY:

40810

AN XY:

633790

show subpopulations

Gnomad4 AFR exome

AF:

0.00878

Gnomad4 AMR exome

AF:

0.0373

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.00471

Gnomad4 SAS exome

AF:

0.127

Gnomad4 FIN exome

AF:

0.0316

Gnomad4 NFE exome

AF:

0.0595

Gnomad4 OTH exome

AF:

0.0659

GnomAD4 genome

AF:

0.0463

AC:

7056

AN:

152270

Hom.:

247

Cov.:

AF XY:

0.0476

AC XY:

3545

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0104

Gnomad4 AMR

AF:

0.0623

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.00773

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.0271

Gnomad4 NFE

AF:

0.0581

Gnomad4 OTH

AF:

0.0653

Alfa

AF:

0.0483

Hom.:

Bravo

AF:

0.0452

Asia WGS

AF:

0.0500

AC:

173

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.1

DANN

Benign

0.47

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over