chr1-156054973-G-A

Variant names:

• chr1-156054973-G-A
• rs1647286365
• NM_014017.4:c.68+16G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_014017.4(LAMTOR2):​c.68+16G>A variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LAMTOR2 NM_014017.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.54
• 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: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 1-156054973-G-A is Benign according to our data. Variant chr1-156054973-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1561473.Status of the report is criteria_provided_single_submitter, 1 stars.

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.68+16G>A		intron	N/A	NP_054736.1	Q9Y2Q5-1
	LAMTOR2	NM_001145264.2		c.68+16G>A		intron	N/A	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.68+16G>A		intron	N/A	ENSP00000357288.4	Q9Y2Q5-1
	LAMTOR2	ENST00000871951.1		c.68+16G>A		intron	N/A	ENSP00000542010.1
	LAMTOR2	ENST00000368302.3	TSL:3	c.68+16G>A		intron	N/A	ENSP00000357285.3	Q9Y2Q5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456874 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724620

African (AFR) AF: 0.00 AC: 0 AN: 33326

American (AMR) AF: 0.00 AC: 0 AN: 44276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39454

South Asian (SAS) AF: 0.00 AC: 0 AN: 85830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5234

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110376

Other (OTH) AF: 0.00 AC: 0 AN: 60166

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	-0.73
CADD	Benign	14
DANN	Benign	0.65
PhyloP100		4.5
PromoterAI		-0.081	Neutral

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: rs1647286365; hg19: chr1-156024764;