2-111898815-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006343.3(MERTK):c.61+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 1,577,290 control chromosomes in the GnomAD database, including 1,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.048 (159 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1453 hom.)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0750

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 2-111898815-G-A is Benign according to our data. Variant chr2-111898815-G-A is described in ClinVar as [Benign]. Clinvar id is 287486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MERTK	NM_006343.3	c.61+19G>A		intron_variant		ENST00000295408.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MERTK	ENST00000295408.9	c.61+19G>A		intron_variant		1	NM_006343.3	P1
MERTK	ENST00000439966.5	c.61+19G>A		intron_variant, NMD_transcript_variant		1
MERTK	ENST00000409780.5	c.-47+19G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7248 AN: 152144 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.0580

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0521

GnomAD3 exomes AF: 0.0396 AC: 6981 AN: 176206 Hom.: 181 AF XY: 0.0388 AC XY: 3751 AN XY: 96774

Gnomad AFR exome AF: 0.0612

Gnomad AMR exome AF: 0.0327

Gnomad ASJ exome AF: 0.0332

Gnomad EAS exome AF: 0.00170

Gnomad SAS exome AF: 0.0216

Gnomad FIN exome AF: 0.0693

Gnomad NFE exome AF: 0.0469

Gnomad OTH exome AF: 0.0437

GnomAD4 exome AF: 0.0427 AC: 60883 AN: 1425028 Hom.: 1453 Cov.: 31 AF XY: 0.0421 AC XY: 29680 AN XY: 705374

Gnomad4 AFR exome AF: 0.0561

Gnomad4 AMR exome AF: 0.0334

Gnomad4 ASJ exome AF: 0.0359

Gnomad4 EAS exome AF: 0.00215

Gnomad4 SAS exome AF: 0.0232

Gnomad4 FIN exome AF: 0.0688

Gnomad4 NFE exome AF: 0.0449

Gnomad4 OTH exome AF: 0.0387

GnomAD4 genome AF: 0.0477 AC: 7257 AN: 152262 Hom.: 159 Cov.: 32 AF XY: 0.0479 AC XY: 3566 AN XY: 74446

Gnomad4 AFR AF: 0.0580

Gnomad4 AMR AF: 0.0376

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.0665

Gnomad4 NFE AF: 0.0467

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0326 Hom.: 19

Bravo AF: 0.0453

Asia WGS AF: 0.0200 AC: 69 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 13, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Retinitis pigmentosa 38 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	7.3
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs115821982; hg19: chr2-112656392;