chr2-112024340-T-C

Variant names:

• chr2-112024340-T-C
• rs13419523
• NM_006343.3:c.2486+1946T>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.2486+1946T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,264 control chromosomes in the GnomAD database, including 1,061 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 0.11 (1061 hom., cov: 32)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594
• Publications: 16 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MERTK	NM_006343.3	c.2486+1946T>C		intron_variant	Intron 18 of 18	ENST00000295408.9	NP_006334.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MERTK	ENST00000295408.9	c.2486+1946T>C		intron_variant	Intron 18 of 18	1	NM_006343.3	ENSP00000295408.4
MERTK	ENST00000439966.5	n.*1959+1946T>C		intron_variant	Intron 18 of 18	1		ENSP00000402129.1
MERTK	ENST00000409780.5	c.1958+1946T>C		intron_variant	Intron 17 of 17	5		ENSP00000387277.1
MERTK	ENST00000449344.2	c.458+1946T>C		intron_variant	Intron 4 of 4	3		ENSP00000412660.2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16079 AN: 152146 Hom.: 1058 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0717

Gnomad ASJ AF: 0.0900

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.0819

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0778

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.106 AC: 16094 AN: 152264 Hom.: 1061 Cov.: 32 AF XY: 0.103 AC XY: 7680 AN XY: 74484

African (AFR) AF: 0.194 AC: 8049 AN: 41522

American (AMR) AF: 0.0717 AC: 1097 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0900 AC: 312 AN: 3468

East Asian (EAS) AF: 0.00443 AC: 23 AN: 5190

South Asian (SAS) AF: 0.0273 AC: 132 AN: 4830

European-Finnish (FIN) AF: 0.0819 AC: 870 AN: 10620

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0778 AC: 5294 AN: 68012

Other (OTH) AF: 0.108 AC: 228 AN: 2116

Alfa AF: 0.0869 Hom.: 1985

Bravo AF: 0.110

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.6
DANN	Benign	0.71
PhyloP100		-0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs13419523; hg19: chr2-112781917; COSMIC: COSV54926720;