rs869016

Variant names:

• chr2-111901533-G-A
• rs869016
• NM_006343.3:c.61+2737G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-111901533-G-A
• chr2-111901533-G-C
• chr2-111901533-G-T

Variant summary

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

The NM_006343.3(MERTK):​c.61+2737G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 150,528 control chromosomes in the GnomAD database, including 9,955 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 0.36 (9955 hom., cov: 29)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 9 publications found

Genes affected

MERTK (HGNC:7027): (MER proto-oncogene, tyrosine kinase) This gene is a member of the MER/AXL/TYRO3 receptor kinase family and encodes a transmembrane protein with two fibronectin type-III domains, two Ig-like C2-type (immunoglobulin-like) domains, and one tyrosine kinase domain. Mutations in this gene have been associated with disruption of the retinal pigment epithelium (RPE) phagocytosis pathway and onset of autosomal recessive retinitis pigmentosa (RP). [provided by RefSeq, Jul 2008]

MERTK Gene-Disease associations (from GenCC):

• MERTK-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 38

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MERTK	NM_006343.3	c.61+2737G>A		intron_variant	Intron 1 of 18	ENST00000295408.9	NP_006334.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MERTK	ENST00000295408.9	c.61+2737G>A		intron_variant	Intron 1 of 18	1	NM_006343.3	ENSP00000295408.4
MERTK	ENST00000439966.5	n.61+2737G>A		intron_variant	Intron 1 of 18	1		ENSP00000402129.1
MERTK	ENST00000409780.5	c.-47+2737G>A		intron_variant	Intron 1 of 17	5		ENSP00000387277.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53467 AN: 150426 Hom.: 9943 Cov.: 29

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.286

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.356 AC: 53515 AN: 150528 Hom.: 9955 Cov.: 29 AF XY: 0.356 AC XY: 26150 AN XY: 73390

African (AFR) AF: 0.292 AC: 11938 AN: 40932

American (AMR) AF: 0.371 AC: 5607 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1098 AN: 3464

East Asian (EAS) AF: 0.733 AC: 3749 AN: 5118

South Asian (SAS) AF: 0.400 AC: 1910 AN: 4770

European-Finnish (FIN) AF: 0.317 AC: 3200 AN: 10096

Middle Eastern (MID) AF: 0.285 AC: 81 AN: 284

European-Non Finnish (NFE) AF: 0.366 AC: 24792 AN: 67762

Other (OTH) AF: 0.352 AC: 735 AN: 2086

Alfa AF: 0.351 Hom.: 3656

Bravo AF: 0.360

Asia WGS AF: 0.518 AC: 1799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.45
DANN	Benign	0.34
PhyloP100		-0.0090
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs869016; hg19: chr2-112659110;