chr2-111898617-C-A

Variant names:

• chr2-111898617-C-A
• rs1224407714
• NM_006343.3:c.-119C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006343.3(MERTK):​c.-119C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,100,488 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: MERTK NM_006343.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006343.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MERTK	NM_006343.3	MANE Select	c.-119C>A		5_prime_UTR	Exon 1 of 19	NP_006334.2	Q12866

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MERTK	ENST00000295408.9	TSL:1 MANE Select	c.-119C>A		5_prime_UTR	Exon 1 of 19	ENSP00000295408.4	Q12866
	MERTK	ENST00000439966.5	TSL:1	n.-119C>A		upstream_gene	N/A	ENSP00000402129.1	E9PD22
	MERTK	ENST00000953051.1		c.-119C>A		upstream_gene	N/A	ENSP00000623110.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1100488 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 554102

African (AFR) AF: 0.00 AC: 0 AN: 24220

American (AMR) AF: 0.00 AC: 0 AN: 34526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22892

East Asian (EAS) AF: 0.00 AC: 0 AN: 33004

South Asian (SAS) AF: 0.00 AC: 0 AN: 71994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4368

European-Non Finnish (NFE) AF: 0.00000246 AC: 2 AN: 814302

Other (OTH) AF: 0.00 AC: 0 AN: 47994

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.66
PhyloP100		-2.2
PromoterAI		0.050	Neutral

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: rs1224407714; hg19: chr2-112656194;