6-41194427-G-A

Variant names:

• chr6-41194427-G-A
• rs773665047
• NM_024807.4:c.783C>T

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.783C>T​(p.Ile261Ile) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00000142 in 1,408,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TREML2 NM_024807.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.8809
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.23
• 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 (BayesDel_noAF=-0.36).

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.783C>T	p.Ile261Ile	splice_region synonymous	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.783C>T	p.Ile261Ile	splice_region synonymous	Exon 3 of 5	ENSP00000418767.1	Q5T2D2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000578 AC: 1 AN: 172922 AF XY: 0.0000109

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1408198 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 695064

African (AFR) AF: 0.00 AC: 0 AN: 32294

American (AMR) AF: 0.00 AC: 0 AN: 36924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24892

East Asian (EAS) AF: 0.00 AC: 0 AN: 36794

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5588

European-Non Finnish (NFE) AF: 9.23e-7 AC: 1 AN: 1082856

Other (OTH) AF: 0.00 AC: 0 AN: 58372

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.73
PhyloP100		4.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.88
dbscSNV1_RF	Benign	0.63
SpliceAI score (max)		0.070		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: rs773665047; hg19: chr6-41162165;