rs786205533

Variant names:

• chr2-111929383-A-G
• NM_006343.3:c.325A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-111929383-A-G
• chr2-111929383-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_006343.3(MERTK):​c.325A>G​(p.Lys109Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MERTK NM_006343.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.93

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 Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a domain Ig-like C2-type 1 (size 105) in uniprot entity MERTK_HUMAN there are 5 pathogenic changes around while only 2 benign (71%) in NM_006343.3
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20152643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MERTK	NM_006343.3	c.325A>G	p.Lys109Glu	missense_variant	Exon 2 of 19	ENST00000295408.9	NP_006334.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MERTK	ENST00000295408.9	c.325A>G	p.Lys109Glu	missense_variant	Exon 2 of 19	1	NM_006343.3	ENSP00000295408.4
MERTK	ENST00000439966.5	n.246+79A>G		intron_variant	Intron 2 of 18	1		ENSP00000402129.1
MERTK	ENST00000409780.5	c.-46-15577A>G		intron_variant	Intron 1 of 17	5		ENSP00000387277.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T;T
Eigen	Benign	0.052
Eigen_PC	Benign	0.056
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.65	.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.044
Sift	Benign	0.044	D;D
Sift4G	Benign	0.24	T;T
Polyphen		0.80	P;P
Vest4		0.43
MutPred		0.38		Loss of ubiquitination at K109 (P = 0.0224);Loss of ubiquitination at K109 (P = 0.0224);
MVP		0.59
MPC		0.59
ClinPred		0.63	D
GERP RS		4.1
Varity_R		0.12
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-112686960;