NM_014017.4:c.111C>T

Variant names:

• chr1-156055305-C-T
• rs7541
• NM_014017.4:c.111C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014017.4(LAMTOR2):​c.111C>T​(p.Tyr37Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,614,022 control chromosomes in the GnomAD database, including 18,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1270 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17389 hom.)
• Consequence: LAMTOR2 NM_014017.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -0.916

Genes affected

LAMTOR2 (HGNC:29796): (late endosomal/lysosomal adaptor, MAPK and MTOR activator 2) The product of this gene is highly conserved with a mouse protein associated with the cytoplasmic face of late endosomes and lysosomes. The mouse protein interacts with MAPK scaffold protein 1, a component of the mitogen-activated protein kinase pathway. In humans, a mutation in this gene has been associated with a primary immunodeficiency syndrome, and suggests a role for this protein in endosomal biogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 1-156055305-C-T is Benign according to our data. Variant chr1-156055305-C-T is described in ClinVar as [Benign]. Clinvar id is 1165734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.916 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMTOR2	NM_014017.4	c.111C>T	p.Tyr37Tyr	synonymous_variant	Exon 2 of 4	ENST00000368305.9	NP_054736.1
LAMTOR2	NM_001145264.2	c.111C>T	p.Tyr37Tyr	synonymous_variant	Exon 2 of 3		NP_001138736.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMTOR2	ENST00000368305.9	c.111C>T	p.Tyr37Tyr	synonymous_variant	Exon 2 of 4	1	NM_014017.4	ENSP00000357288.4

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17942 AN: 152098 Hom.: 1270 Cov.: 32

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0749

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.141

GnomAD3 exomes AF: 0.121 AC: 30534 AN: 251426 Hom.: 2283 AF XY: 0.125 AC XY: 16964 AN XY: 135908

Gnomad AFR exome AF: 0.0514

Gnomad AMR exome AF: 0.0909

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0814

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.148 AC: 216741 AN: 1461806 Hom.: 17389 Cov.: 32 AF XY: 0.147 AC XY: 107139 AN XY: 727218

Gnomad4 AFR exome AF: 0.0508

Gnomad4 AMR exome AF: 0.0944

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.0841

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.118 AC: 17934 AN: 152216 Hom.: 1270 Cov.: 32 AF XY: 0.118 AC XY: 8754 AN XY: 74430

Gnomad4 AFR AF: 0.0521

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0745

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.139

Alfa AF: 0.143 Hom.: 950

Bravo AF: 0.115

Asia WGS AF: 0.0380 AC: 133 AN: 3478

EpiCase AF: 0.166

EpiControl AF: 0.166

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3 Other:1

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.2
DANN	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs7541; hg19: chr1-156025096; COSMIC: COSV64145997; COSMIC: COSV64145997;