rs7541

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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]

LAMTOR2 Gene-Disease associations (from GenCC):

• primary immunodeficiency syndrome due to p14 deficiency

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014017.4. 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
	LAMTOR2	NM_014017.4	MANE Select	c.111C>T	p.Tyr37Tyr	synonymous	Exon 2 of 4	NP_054736.1	Q9Y2Q5-1
	LAMTOR2	NM_001145264.2		c.111C>T	p.Tyr37Tyr	synonymous	Exon 2 of 3	NP_001138736.1	Q9Y2Q5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMTOR2	ENST00000368305.9	TSL:1 MANE Select	c.111C>T	p.Tyr37Tyr	synonymous	Exon 2 of 4	ENSP00000357288.4	Q9Y2Q5-1
	LAMTOR2	ENST00000871951.1		c.111C>T	p.Tyr37Tyr	synonymous	Exon 2 of 5	ENSP00000542010.1
	LAMTOR2	ENST00000368302.3	TSL:3	c.111C>T	p.Tyr37Tyr	synonymous	Exon 2 of 4	ENSP00000357285.3	Q9Y2Q5-2

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

GnomAD2 exomes AF: 0.121 AC: 30534 AN: 251426 AF XY: 0.125

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 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

African (AFR) AF: 0.0508 AC: 1700 AN: 33480

American (AMR) AF: 0.0944 AC: 4223 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 4035 AN: 26136

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39700

South Asian (SAS) AF: 0.0841 AC: 7255 AN: 86258

European-Finnish (FIN) AF: 0.150 AC: 8001 AN: 53370

Middle Eastern (MID) AF: 0.191 AC: 1102 AN: 5768

European-Non Finnish (NFE) AF: 0.163 AC: 181605 AN: 1111978

Other (OTH) AF: 0.146 AC: 8808 AN: 60392

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

African (AFR) AF: 0.0521 AC: 2166 AN: 41542

American (AMR) AF: 0.120 AC: 1842 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 553 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5174

South Asian (SAS) AF: 0.0745 AC: 360 AN: 4830

European-Finnish (FIN) AF: 0.144 AC: 1521 AN: 10594

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10897 AN: 67996

Other (OTH) AF: 0.139 AC: 294 AN: 2114

Alfa AF: 0.143 Hom.: 951

Bravo AF: 0.115

Asia WGS AF: 0.0380 AC: 133 AN: 3478

EpiCase AF: 0.166

EpiControl AF: 0.166

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (4)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.2
DANN	Benign	0.94
PhyloP100		-0.92
PromoterAI		-0.042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs7541; hg19: chr1-156025096; COSMIC: COSV64145997; COSMIC: COSV64145997;