6-41192881-G-C

Variant names:

• chr6-41192881-G-C
• rs774938098
• NM_024807.4:c.806C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024807.4(TREML2):​c.806C>G​(p.Thr269Ser) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T269I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TREML2 NM_024807.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.389
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.071074784).

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.806C>G	p.Thr269Ser	missense	Exon 4 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.806C>G	p.Thr269Ser	missense	Exon 4 of 5	ENSP00000418767.1	Q5T2D2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.6
DANN	Benign	0.85
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.39
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.026
Sift	Benign	0.070	T
Sift4G	Benign	0.37	T
Polyphen		0.062	B
Vest4		0.075
MutPred		0.28		Gain of disorder (P = 0.0562)
MVP		0.27
MPC		0.21
ClinPred		0.084	T
GERP RS		1.4
Varity_R		0.093
gMVP		0.16
Mutation Taster		=98/2	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: rs774938098; hg19: chr6-41160619;