chr2-112026380-A-G

Variant names:

• chr2-112026380-A-G
• rs6730521
• NM_006343.3:c.2487-1971A>G

Variant summary

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

The NM_006343.3(MERTK):​c.2487-1971A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,144 control chromosomes in the GnomAD database, including 4,493 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 0.23 (4493 hom., cov: 32)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717
• Publications: 15 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=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.304 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MERTK	NM_006343.3	MANE Select	c.2487-1971A>G		intron	N/A	NP_006334.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MERTK	ENST00000295408.9	TSL:1 MANE Select	c.2487-1971A>G		intron	N/A	ENSP00000295408.4
	MERTK	ENST00000439966.5	TSL:1	n.*1960-1971A>G		intron	N/A	ENSP00000402129.1
	MERTK	ENST00000409780.5	TSL:5	c.1959-1971A>G		intron	N/A	ENSP00000387277.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35566 AN: 152026 Hom.: 4486 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.234 AC: 35593 AN: 152144 Hom.: 4493 Cov.: 32 AF XY: 0.241 AC XY: 17956 AN XY: 74400

African (AFR) AF: 0.175 AC: 7273 AN: 41508

American (AMR) AF: 0.286 AC: 4374 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3470

East Asian (EAS) AF: 0.106 AC: 551 AN: 5182

South Asian (SAS) AF: 0.317 AC: 1527 AN: 4816

European-Finnish (FIN) AF: 0.385 AC: 4071 AN: 10582

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16340 AN: 67984

Other (OTH) AF: 0.198 AC: 419 AN: 2116

Alfa AF: 0.231 Hom.: 4293

Bravo AF: 0.223

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.90
PhyloP100		0.72
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: rs6730521; hg19: chr2-112783957;