rs1187272

Variant names:

• chr9-84789171-G-A
• rs1187272
• NM_006180.6:c.1396+37086G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-84789171-G-A
• chr9-84789171-G-C
• chr9-84789171-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006180.6(NTRK2):​c.1396+37086G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,950 control chromosomes in the GnomAD database, including 27,280 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 0.58 (27280 hom., cov: 31)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412
• Publications: 6 publications found

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]

NTRK2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 58

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• obesity, hyperphagia, and developmental delay

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1396+37086G>A		intron_variant	Intron 12 of 18	ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1396+37086G>A		intron_variant	Intron 12 of 18	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88297 AN: 151832 Hom.: 27300 Cov.: 31

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.581 AC: 88285 AN: 151950 Hom.: 27280 Cov.: 31 AF XY: 0.586 AC XY: 43535 AN XY: 74250

African (AFR) AF: 0.358 AC: 14837 AN: 41406

American (AMR) AF: 0.613 AC: 9364 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2286 AN: 3470

East Asian (EAS) AF: 0.675 AC: 3477 AN: 5150

South Asian (SAS) AF: 0.682 AC: 3282 AN: 4812

European-Finnish (FIN) AF: 0.742 AC: 7836 AN: 10562

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45238 AN: 67968

Other (OTH) AF: 0.596 AC: 1255 AN: 2106

Alfa AF: 0.498 Hom.: 1660

Bravo AF: 0.559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.2
DANN	Benign	0.64
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1187272; hg19: chr9-87404086;