2-112013193-A-G

Position:

• chr2-112013193-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006343.3(MERTK):​c.2079+3127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 153,820 control chromosomes in the GnomAD database, including 26,210 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 0.58 (25816 hom., cov: 29)
  • Exomes 𝑓: 0.61 (394 hom.)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MERTK	NM_006343.3	c.2079+3127A>G		intron_variant		ENST00000295408.9	NP_006334.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MERTK	ENST00000295408.9	c.2079+3127A>G		intron_variant		1	NM_006343.3	ENSP00000295408	P1
MERTK	ENST00000439966.5	c.*1552+3127A>G		intron_variant, NMD_transcript_variant		1		ENSP00000402129
MERTK	ENST00000409780.5	c.1551+3127A>G		intron_variant		5		ENSP00000387277

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87780 AN: 151646 Hom.: 25798 Cov.: 29

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.596

GnomAD4 exome AF: 0.612 AC: 1258 AN: 2056 Hom.: 394 Cov.: 0 AF XY: 0.598 AC XY: 614 AN XY: 1026

Gnomad4 AFR exome AF: 0.614

Gnomad4 AMR exome AF: 0.750

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.670

Gnomad4 NFE exome AF: 0.620

Gnomad4 OTH exome AF: 0.551

GnomAD4 genome AF: 0.579 AC: 87838 AN: 151764 Hom.: 25816 Cov.: 29 AF XY: 0.580 AC XY: 43013 AN XY: 74120

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.598

Alfa AF: 0.606 Hom.: 36128

Bravo AF: 0.568

Asia WGS AF: 0.469 AC: 1633 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	3.2
DANN	Benign	0.70

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: rs4374383; hg19: chr2-112770770;