rs2234250

Positions:

• chr6-41162955-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018965.4(TREM2):​c.40+88T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.004 in 1,581,948 control chromosomes in the GnomAD database, including 182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (87 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (95 hom.)
• Consequence: TREM2 NM_018965.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.129

Genes affected

TREM2 (HGNC:17761): (triggering receptor expressed on myeloid cells 2) This gene encodes a membrane protein that forms a receptor signaling complex with the TYRO protein tyrosine kinase binding protein. The encoded protein functions in immune response and may be involved in chronic inflammation by triggering the production of constitutive inflammatory cytokines. Defects in this gene are a cause of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-41162955-A-G is Benign according to our data. Variant chr6-41162955-A-G is described in ClinVar as [Benign]. Clinvar id is 1182120.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREM2	NM_018965.4	c.40+88T>C		intron_variant		ENST00000373113.8	NP_061838.1
TREM2	NM_001271821.2	c.40+88T>C		intron_variant			NP_001258750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREM2	ENST00000373113.8	c.40+88T>C		intron_variant		1	NM_018965.4	ENSP00000362205	P1
TREM2	ENST00000338469.3	c.40+88T>C		intron_variant		1		ENSP00000342651
TREM2	ENST00000373122.8	c.40+88T>C		intron_variant		1		ENSP00000362214
	ENST00000702590.1	n.364+7392A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2838 AN: 151822 Hom.: 89 Cov.: 32

Gnomad AFR AF: 0.0636

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00879

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0106

GnomAD4 exome AF: 0.00244 AC: 3491 AN: 1430006 Hom.: 95 AF XY: 0.00223 AC XY: 1589 AN XY: 713126

Gnomad4 AFR exome AF: 0.0686

Gnomad4 AMR exome AF: 0.00490

Gnomad4 ASJ exome AF: 0.000965

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000351

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000549

Gnomad4 OTH exome AF: 0.00526

GnomAD4 genome AF: 0.0187 AC: 2840 AN: 151942 Hom.: 87 Cov.: 32 AF XY: 0.0184 AC XY: 1370 AN XY: 74274

Gnomad4 AFR AF: 0.0635

Gnomad4 AMR AF: 0.00878

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00432 Hom.: 15

Bravo AF: 0.0214

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 14, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs2234250; hg19: chr6-41130693;