6-41194459-G-T

Variant names:

• chr6-41194459-G-T
• rs185375765
• NM_024807.4:c.751C>A

Variant summary

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

The NM_024807.4(TREML2):​c.751C>A​(p.Leu251Ile) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L251V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: TREML2 NM_024807.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 0 publications found

Genes affected

TREML2 (HGNC:21092): (triggering receptor expressed on myeloid cells like 2) TREML2 is located in a gene cluster on chromosome 6 with the single Ig variable (IgV) domain activating receptors TREM1 (MIM 605085) and TREM2 (MIM 605086), but it has distinct structural and functional properties (Allcock et al., 2003 [PubMed 12645956]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05999449).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024807.4. 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
	TREML2	NM_024807.4	MANE Select	c.751C>A	p.Leu251Ile	missense	Exon 3 of 5	NP_079083.2	Q5T2D2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREML2	ENST00000483722.2	TSL:1 MANE Select	c.751C>A	p.Leu251Ile	missense	Exon 3 of 5	ENSP00000418767.1	Q5T2D2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.057
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.042
Sift	Uncertain	0.027	D
Sift4G	Benign	0.093	T
Polyphen		0.27	B
Vest4		0.16
MutPred		0.18		Gain of glycosylation at S248 (P = 0.0981)
MVP		0.12
MPC		0.66
ClinPred		0.087	T
GERP RS		0.83
Varity_R		0.044
gMVP		0.076
Mutation Taster		=99/1	polymorphism

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: rs185375765; hg19: chr6-41162197;