2-112009829-A-G

Variant names:

• chr2-112009829-A-G
• rs11884641
• NM_006343.3:c.1961-119A>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.1961-119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 817,702 control chromosomes in the GnomAD database, including 30,071 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 0.25 (4981 hom., cov: 32)
  • Exomes 𝑓: 0.26 (25090 hom.)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 21 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MERTK	NM_006343.3	c.1961-119A>G		intron_variant	Intron 14 of 18	ENST00000295408.9	NP_006334.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MERTK	ENST00000295408.9	c.1961-119A>G		intron_variant	Intron 14 of 18	1	NM_006343.3	ENSP00000295408.4
MERTK	ENST00000439966.5	n.*1434-119A>G		intron_variant	Intron 14 of 18	1		ENSP00000402129.1
MERTK	ENST00000409780.5	c.1433-119A>G		intron_variant	Intron 13 of 17	5		ENSP00000387277.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37813 AN: 151722 Hom.: 4971 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.263 AC: 175109 AN: 665862 Hom.: 25090 AF XY: 0.264 AC XY: 95040 AN XY: 360296

African (AFR) AF: 0.223 AC: 3978 AN: 17852

American (AMR) AF: 0.398 AC: 16815 AN: 42266

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 4395 AN: 20466

East Asian (EAS) AF: 0.109 AC: 3815 AN: 35092

South Asian (SAS) AF: 0.327 AC: 22701 AN: 69502

European-Finnish (FIN) AF: 0.374 AC: 17502 AN: 46802

Middle Eastern (MID) AF: 0.202 AC: 827 AN: 4102

European-Non Finnish (NFE) AF: 0.244 AC: 96685 AN: 396164

Other (OTH) AF: 0.250 AC: 8391 AN: 33616

GnomAD4 genome AF: 0.249 AC: 37843 AN: 151840 Hom.: 4981 Cov.: 32 AF XY: 0.256 AC XY: 19010 AN XY: 74192

African (AFR) AF: 0.223 AC: 9214 AN: 41362

American (AMR) AF: 0.298 AC: 4552 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 799 AN: 3472

East Asian (EAS) AF: 0.103 AC: 530 AN: 5166

South Asian (SAS) AF: 0.325 AC: 1557 AN: 4792

European-Finnish (FIN) AF: 0.387 AC: 4077 AN: 10524

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

European-Non Finnish (NFE) AF: 0.241 AC: 16408 AN: 67960

Other (OTH) AF: 0.211 AC: 444 AN: 2104

Alfa AF: 0.240 Hom.: 15317

Bravo AF: 0.240

Asia WGS AF: 0.208 AC: 726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.33
PhyloP100		-1.2
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: rs11884641; hg19: chr2-112767406; COSMIC: COSV54930023;