chr15-28014717-A-G

Variant names:

• chr15-28014717-A-G
• rs4640131
• NM_000275.3:c.1044+59T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000275.3(OCA2):​c.1044+59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,584,610 control chromosomes in the GnomAD database, including 5,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1269 hom., cov: 32)
  • Exomes 𝑓: 0.060 (3842 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.375
• 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: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-28014717-A-G is Benign according to our data. Variant chr15-28014717-A-G is described in ClinVar as Benign. ClinVar VariationId is 1285944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 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.1044+59T>C		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.1044+59T>C		intron	N/A	NP_001287913.1	Q04671-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.1044+59T>C		intron	N/A	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.1044+59T>C		intron	N/A	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.1044+59T>C		intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15374 AN: 152068 Hom.: 1249 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0708

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00829

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0310

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0507

Gnomad OTH AF: 0.0947

GnomAD4 exome AF: 0.0605 AC: 86653 AN: 1432424 Hom.: 3842 AF XY: 0.0629 AC XY: 44823 AN XY: 712668

African (AFR) AF: 0.222 AC: 7324 AN: 33012

American (AMR) AF: 0.0422 AC: 1835 AN: 43458

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 4005 AN: 25768

East Asian (EAS) AF: 0.00458 AC: 179 AN: 39096

South Asian (SAS) AF: 0.141 AC: 11901 AN: 84204

European-Finnish (FIN) AF: 0.0322 AC: 1377 AN: 42702

Middle Eastern (MID) AF: 0.128 AC: 699 AN: 5462

European-Non Finnish (NFE) AF: 0.0499 AC: 54845 AN: 1099132

Other (OTH) AF: 0.0753 AC: 4488 AN: 59590

GnomAD4 genome AF: 0.101 AC: 15427 AN: 152186 Hom.: 1269 Cov.: 32 AF XY: 0.101 AC XY: 7543 AN XY: 74400

African (AFR) AF: 0.217 AC: 9020 AN: 41488

American (AMR) AF: 0.0706 AC: 1079 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3470

East Asian (EAS) AF: 0.00831 AC: 43 AN: 5172

South Asian (SAS) AF: 0.144 AC: 693 AN: 4816

European-Finnish (FIN) AF: 0.0310 AC: 329 AN: 10614

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0507 AC: 3449 AN: 68016

Other (OTH) AF: 0.0938 AC: 198 AN: 2112

Alfa AF: 0.0705 Hom.: 712

Bravo AF: 0.107

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.27
PhyloP100		-0.38
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: rs4640131; hg19: chr15-28259863;