2-111917281-G-A

Variant names:

• chr2-111917281-G-A
• rs1516640
• NM_006343.3:c.62-11839G>A

Variant summary

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

The NM_006343.3(MERTK):​c.62-11839G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,928 control chromosomes in the GnomAD database, including 16,520 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 0.46 (16520 hom., cov: 31)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006343.3. 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
	MERTK	NM_006343.3	MANE Select	c.62-11839G>A		intron	N/A	NP_006334.2	Q12866

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MERTK	ENST00000295408.9	TSL:1 MANE Select	c.62-11839G>A		intron	N/A	ENSP00000295408.4	Q12866
	MERTK	ENST00000439966.5	TSL:1	n.62-11839G>A		intron	N/A	ENSP00000402129.1	E9PD22
	MERTK	ENST00000953051.1		c.62-11839G>A		intron	N/A	ENSP00000623110.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70448 AN: 151810 Hom.: 16504 Cov.: 31

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.464 AC: 70506 AN: 151928 Hom.: 16520 Cov.: 31 AF XY: 0.462 AC XY: 34288 AN XY: 74232

African (AFR) AF: 0.440 AC: 18241 AN: 41430

American (AMR) AF: 0.460 AC: 7031 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1657 AN: 3470

East Asian (EAS) AF: 0.737 AC: 3798 AN: 5156

South Asian (SAS) AF: 0.441 AC: 2123 AN: 4812

European-Finnish (FIN) AF: 0.414 AC: 4365 AN: 10550

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31560 AN: 67914

Other (OTH) AF: 0.471 AC: 993 AN: 2110

Alfa AF: 0.462 Hom.: 9500

Bravo AF: 0.471

Asia WGS AF: 0.555 AC: 1928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.72
DANN	Benign	0.73
PhyloP100		-1.2
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: rs1516640; hg19: chr2-112674858; COSMIC: COSV54926437;