chr2-111971234-C-G

Variant names:

• chr2-111971234-C-G
• rs4434006
• NM_006343.3:c.960+2982C>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.960+2982C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 151,936 control chromosomes in the GnomAD database, including 4,650 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 0.24 (4650 hom., cov: 32)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.538
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

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.960+2982C>G		intron	N/A	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.960+2982C>G		intron	N/A	ENSP00000295408.4	Q12866
	MERTK	ENST00000439966.5	TSL:1	n.*433+2982C>G		intron	N/A	ENSP00000402129.1	E9PD22
	MERTK	ENST00000953051.1		c.960+2982C>G		intron	N/A	ENSP00000623110.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36140 AN: 151818 Hom.: 4641 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.238 AC: 36168 AN: 151936 Hom.: 4650 Cov.: 32 AF XY: 0.245 AC XY: 18193 AN XY: 74262

African (AFR) AF: 0.187 AC: 7761 AN: 41480

American (AMR) AF: 0.292 AC: 4457 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 758 AN: 3468

East Asian (EAS) AF: 0.103 AC: 534 AN: 5174

South Asian (SAS) AF: 0.324 AC: 1560 AN: 4814

European-Finnish (FIN) AF: 0.386 AC: 4035 AN: 10466

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

European-Non Finnish (NFE) AF: 0.241 AC: 16379 AN: 67948

Other (OTH) AF: 0.200 AC: 422 AN: 2110

Alfa AF: 0.156 Hom.: 332

Bravo AF: 0.227

Asia WGS AF: 0.204 AC: 708 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.55
PhyloP100		0.54
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: rs4434006; hg19: chr2-112728811;