5-138874383-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015564.3(LRRTM2):c.178G>A(p.Asp60Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LRRTM2
NM_015564.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.16

Variant links:

Genes affected

LRRTM2 (HGNC:19409): (leucine rich repeat transmembrane neuronal 2) Predicted to enable neurexin family protein binding activity. Predicted to be involved in regulation of postsynaptic density assembly. Predicted to act upstream of or within several processes, including long-term synaptic potentiation; negative regulation of receptor internalization; and positive regulation of synapse assembly. Is active in GABA-ergic synapse. Is integral component of postsynaptic specialization membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRTM2 links:

CTNNA1 (HGNC:2509): (catenin alpha 1) This gene encodes a member of the catenin family of proteins that play an important role in cell adhesion process by connecting cadherins located on the plasma membrane to the actin filaments inside the cell. The encoded mechanosensing protein contains three vinculin homology domains and undergoes conformational changes in response to cytoskeletal tension, resulting in the reconfiguration of cadherin-actin filament connections. Certain mutations in this gene cause butterfly-shaped pigment dystrophy. [provided by RefSeq, May 2016]

CTNNA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16460496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRTM2	NM_015564.3 link	c.178G>A	p.Asp60Asn	missense_variant	Exon 2 of 2	ENST00000274711.7	NP_056379.1	O43300
CTNNA1	NM_001903.5 link	c.1063-11829C>T		intron_variant	Intron 7 of 17	ENST00000302763.12	NP_001894.2	P35221-1A0A384MDY0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRTM2	ENST00000274711.7 link	c.178G>A	p.Asp60Asn	missense_variant	Exon 2 of 2	1	NM_015564.3	ENSP00000274711.5		O43300
CTNNA1	ENST00000302763.12 link	c.1063-11829C>T		intron_variant	Intron 7 of 17	1	NM_001903.5	ENSP00000304669.7		P35221-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.0000264

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.178G>A (p.D60N) alteration is located in exon 2 (coding exon 2) of the LRRTM2 gene. This alteration results from a G to A substitution at nucleotide position 178, causing the aspartic acid (D) at amino acid position 60 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

Eigen

Benign

0.015

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0053

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.30

REVEL

Benign

0.053

Sift

Benign

0.044

Sift4G

Uncertain

0.051

Polyphen

0.028

Vest4

0.40

MutPred

0.45

Loss of ubiquitination at K61 (P = 0.1041);

MVP

0.17

MPC

0.51

ClinPred

0.77

GERP RS

5.1

Varity_R

0.22

gMVP

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over