rs11140777

chr9-84832046-T-Cchr9-84832046-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006180.6(NTRK2):c.1397-28994T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,092 control chromosomes in the GnomAD database, including 19,172 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (19172 hom., cov: 33)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250

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]

LOC124902193 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.1397-28994T>C		intron_variant		ENST00000277120.8
LOC124902193	XR_007061632.1	n.22A>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.1397-28994T>C		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75908 AN: 151974 Hom.: 19141 Cov.: 33

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.494

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.500 AC: 75991 AN: 152092 Hom.: 19172 Cov.: 33 AF XY: 0.494 AC XY: 36718 AN XY: 74338

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.498

Alfa AF: 0.493 Hom.: 2277

Bravo AF: 0.505

Asia WGS AF: 0.450 AC: 1564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.9
Dann	Benign	0.57

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: rs11140777; hg19: chr9-87446961; COSMIC: COSV99452015;