NM_006343.3:c.2079+1348G>A

Variant names:

• chr2-112011414-G-A
• rs12469210
• NM_006343.3:c.2079+1348G>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.2079+1348G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,994 control chromosomes in the GnomAD database, including 4,961 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 0.25 (4961 hom., cov: 32)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 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.2079+1348G>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.2079+1348G>A		intron	N/A	ENSP00000295408.4	Q12866
	MERTK	ENST00000439966.5	TSL:1	n.*1552+1348G>A		intron	N/A	ENSP00000402129.1	E9PD22
	MERTK	ENST00000953051.1		c.1998+1348G>A		intron	N/A	ENSP00000623110.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37716 AN: 151876 Hom.: 4951 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.248 AC: 37746 AN: 151994 Hom.: 4961 Cov.: 32 AF XY: 0.255 AC XY: 18958 AN XY: 74272

African (AFR) AF: 0.222 AC: 9213 AN: 41440

American (AMR) AF: 0.293 AC: 4482 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3470

East Asian (EAS) AF: 0.102 AC: 530 AN: 5174

South Asian (SAS) AF: 0.323 AC: 1553 AN: 4806

European-Finnish (FIN) AF: 0.386 AC: 4074 AN: 10546

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16393 AN: 67974

Other (OTH) AF: 0.209 AC: 441 AN: 2108

Alfa AF: 0.251 Hom.: 749

Bravo AF: 0.239

Asia WGS AF: 0.208 AC: 726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.58
PhyloP100		0.079
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: rs12469210; hg19: chr2-112768991;