chr2-111912373-A-G

Variant names:

• chr2-111912373-A-G
• rs7568632
• NM_006343.3:c.61+13577A>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.61+13577A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,034 control chromosomes in the GnomAD database, including 4,054 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 0.22 (4054 hom., cov: 32)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MERTK	NM_006343.3	c.61+13577A>G		intron_variant	Intron 1 of 18	ENST00000295408.9	NP_006334.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MERTK	ENST00000295408.9	c.61+13577A>G		intron_variant	Intron 1 of 18	1	NM_006343.3	ENSP00000295408.4
MERTK	ENST00000439966.5	n.61+13577A>G		intron_variant	Intron 1 of 18	1		ENSP00000402129.1
MERTK	ENST00000409780.5	c.-47+13577A>G		intron_variant	Intron 1 of 17	5		ENSP00000387277.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32756 AN: 151916 Hom.: 4049 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0816

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.216 AC: 32768 AN: 152034 Hom.: 4054 Cov.: 32 AF XY: 0.223 AC XY: 16537 AN XY: 74272

African (AFR) AF: 0.122 AC: 5062 AN: 41486

American (AMR) AF: 0.261 AC: 3986 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 762 AN: 3468

East Asian (EAS) AF: 0.0814 AC: 421 AN: 5172

South Asian (SAS) AF: 0.315 AC: 1519 AN: 4822

European-Finnish (FIN) AF: 0.385 AC: 4055 AN: 10542

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

European-Non Finnish (NFE) AF: 0.240 AC: 16314 AN: 67966

Other (OTH) AF: 0.183 AC: 387 AN: 2112

Alfa AF: 0.224 Hom.: 4901

Bravo AF: 0.199

Asia WGS AF: 0.188 AC: 656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.73
PhyloP100		-0.16
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: rs7568632; hg19: chr2-112669950;