2-111953251-T-C

Position:

• chr2-111953251-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MERTK	NM_006343.3	c.757+5684T>C		intron_variant		ENST00000295408.9	NP_006334.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MERTK	ENST00000295408.9	c.757+5684T>C		intron_variant		1	NM_006343.3	ENSP00000295408.4
MERTK	ENST00000439966.5	n.*230+5684T>C		intron_variant		1		ENSP00000402129.1
MERTK	ENST00000409780.5	c.229+5684T>C		intron_variant		5		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

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.522

Alfa AF: 0.514 Hom.: 8290

Bravo AF: 0.515

Asia WGS AF: 0.435 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.39
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs4848901; hg19: chr2-112710828;