6-41194562-G-T

Position:

• chr6-41194562-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024807.4(TREML2):​c.648C>A​(p.Ser216Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: TREML2 NM_024807.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.791

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047799915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREML2	NM_024807.4	c.648C>A	p.Ser216Arg	missense_variant	3/5	ENST00000483722.2	NP_079083.2
TREML2	XM_011514917.3	c.327C>A	p.Ser109Arg	missense_variant	2/4		XP_011513219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREML2	ENST00000483722.2	c.648C>A	p.Ser216Arg	missense_variant	3/5	1	NM_024807.4	ENSP00000418767	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.648C>A (p.S216R) alteration is located in exon 3 (coding exon 3) of the TREML2 gene. This alteration results from a C to A substitution at nucleotide position 648, causing the serine (S) at amino acid position 216 to be replaced by an arginine (R). 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	0.21
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.84
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.040
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.31	T
Polyphen		0.011	B
Vest4		0.12
MutPred		0.25		Gain of sheet (P = 0.0036);
MVP		0.18
MPC		0.25
ClinPred		0.12	T
GERP RS		1.7
Varity_R		0.11
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-41162300;