2-111953251-T-C

Variant names:

• chr2-111953251-T-C
• rs4848901
• NM_006343.3:c.757+5684T>C

Variant summary

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

The NM_006343.3(MERTK):​c.757+5684T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,080 control chromosomes in the GnomAD database, including 21,040 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 0.52 (21040 hom., cov: 32)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.54 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.757+5684T>C		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.757+5684T>C		intron	N/A	ENSP00000295408.4
	MERTK	ENST00000439966.5	TSL:1	n.*230+5684T>C		intron	N/A	ENSP00000402129.1
	MERTK	ENST00000409780.5	TSL:5	c.229+5684T>C		intron	N/A	ENSP00000387277.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79603 AN: 151962 Hom.: 21025 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.524 AC: 79665 AN: 152080 Hom.: 21040 Cov.: 32 AF XY: 0.526 AC XY: 39070 AN XY: 74344

African (AFR) AF: 0.516 AC: 21409 AN: 41462

American (AMR) AF: 0.533 AC: 8150 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1837 AN: 3470

East Asian (EAS) AF: 0.255 AC: 1321 AN: 5180

South Asian (SAS) AF: 0.558 AC: 2693 AN: 4826

European-Finnish (FIN) AF: 0.586 AC: 6192 AN: 10568

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36493 AN: 67974

Other (OTH) AF: 0.522 AC: 1104 AN: 2114

Alfa AF: 0.516 Hom.: 9497

Bravo AF: 0.515

Asia WGS AF: 0.435 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.39
DANN	Benign	0.53
PhyloP100		-1.3
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: rs4848901; hg19: chr2-112710828;