9-84670680-C-G

Variant summary

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

The NM_006180.6(NTRK2):c.-69C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,533,026 control chromosomes in the GnomAD database, including 241,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (20242 hom., cov: 33)
  • Exomes 𝑓: 0.56 (220997 hom.)
• Consequence: NTRK2 NM_006180.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.423

Genes affected

NTRK2 (HGNC:8032): (neurotrophic receptor tyrosine kinase 2) This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation. Mutations in this gene have been associated with obesity and mood disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 9-84670680-C-G is Benign according to our data. Variant chr9-84670680-C-G is described in ClinVar as [Benign]. Clinvar id is 1295965.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.-69C>G		5_prime_UTR_variant	2/19	ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.-69C>G		5_prime_UTR_variant	2/19	1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76229 AN: 152040 Hom.: 20240 Cov.: 33

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.508

GnomAD4 exome AF: 0.563 AC: 777723 AN: 1380870 Hom.: 220997 Cov.: 22 AF XY: 0.563 AC XY: 388945 AN XY: 690728

Gnomad4 AFR exome AF: 0.305

Gnomad4 AMR exome AF: 0.648

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.584

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.626

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.550

GnomAD4 genome AF: 0.501 AC: 76245 AN: 152156 Hom.: 20242 Cov.: 33 AF XY: 0.506 AC XY: 37653 AN XY: 74416

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.503

Alfa AF: 0.404 Hom.: 1192

Bravo AF: 0.485

Asia WGS AF: 0.505 AC: 1758 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

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	7.4
Dann	Benign	0.82

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: rs1187325; hg19: chr9-87285595; COSMIC: COSV52861221;