9-84670322-A-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.-372-55A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 295,420 control chromosomes in the GnomAD database, including 719 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.069 (560 hom., cov: 32)
  • Exomes 𝑓: 0.037 (159 hom.)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.292

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=-0.83).
• BP6: Variant 9-84670322-A-G is Benign according to our data. Variant chr9-84670322-A-G is described in ClinVar as [Benign]. Clinvar id is 1246961.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.-372-55A>G		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.-372-55A>G		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.0690 AC: 10486 AN: 151926 Hom.: 559 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.0185

Gnomad EAS AF: 0.0321

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.0617

GnomAD4 exome AF: 0.0368 AC: 5272 AN: 143374 Hom.: 159 AF XY: 0.0353 AC XY: 2464 AN XY: 69768

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.0620

Gnomad4 ASJ exome AF: 0.0238

Gnomad4 EAS exome AF: 0.0345

Gnomad4 SAS exome AF: 0.0143

Gnomad4 FIN exome AF: 0.0291

Gnomad4 NFE exome AF: 0.0329

Gnomad4 OTH exome AF: 0.0436

GnomAD4 genome AF: 0.0691 AC: 10508 AN: 152046 Hom.: 560 Cov.: 32 AF XY: 0.0676 AC XY: 5028 AN XY: 74324

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0677

Gnomad4 ASJ AF: 0.0185

Gnomad4 EAS AF: 0.0320

Gnomad4 SAS AF: 0.0162

Gnomad4 FIN AF: 0.0325

Gnomad4 NFE AF: 0.0348

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0569 Hom.: 33

Bravo AF: 0.0767

Asia WGS AF: 0.0330 AC: 113 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

Jun 20, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.1
Dann	Benign	0.37

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: rs45554739; hg19: chr9-87285237;