NM_014017.4:c.66C>G

Variant names:

• chr1-156054955-C-G
• NM_014017.4:c.66C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_014017.4(LAMTOR2):​c.66C>G​(p.Thr22Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LAMTOR2 NM_014017.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.005095
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0760
• Publications: 0 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: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 1-156054955-C-G is Benign according to our data. Variant chr1-156054955-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3680298.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.076 with no splicing effect.

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.66C>G	p.Thr22Thr	splice_region synonymous	Exon 1 of 4	NP_054736.1	Q9Y2Q5-1
	LAMTOR2	NM_001145264.2		c.66C>G	p.Thr22Thr	splice_region synonymous	Exon 1 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.66C>G	p.Thr22Thr	splice_region synonymous	Exon 1 of 4	ENSP00000357288.4	Q9Y2Q5-1
	LAMTOR2	ENST00000871951.1		c.66C>G	p.Thr22Thr	splice_region synonymous	Exon 1 of 5	ENSP00000542010.1
	LAMTOR2	ENST00000368302.3	TSL:3	c.66C>G	p.Thr22Thr	splice_region synonymous	Exon 1 of 4	ENSP00000357285.3	Q9Y2Q5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		-0.076
PromoterAI		-0.046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0051
dbscSNV1_RF	Benign	0.11
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

hg19: chr1-156024746;