rs1187323

Variant names:

• chr9-84668501-C-A
• rs1187323
• ENST00000685209.1:n.127C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-84668501-C-A
• chr9-84668501-C-G
• chr9-84668501-C-T

Variant summary

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

The ENST00000685209.1(NTRK2):​n.127C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,202 control chromosomes in the GnomAD database, including 49,132 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 0.80 (49131 hom., cov: 34)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: NTRK2 ENST00000685209.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 17 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_001369532.1	c.-866C>A		upstream_gene_variant			NP_001356461.1
NTRK2	NM_001369533.1	c.-657C>A		upstream_gene_variant			NP_001356462.1
NTRK2	NM_001369537.1	c.-746C>A		upstream_gene_variant			NP_001356466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000685209.1	n.127C>A		non_coding_transcript_exon_variant	Exon 1 of 16
NTRK2	ENST00000686332.1	n.127C>A		non_coding_transcript_exon_variant	Exon 1 of 17
NTRK2	ENST00000689651.1	n.127C>A		non_coding_transcript_exon_variant	Exon 1 of 14

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122086 AN: 152078 Hom.: 49093 Cov.: 34

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.813

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 4 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.803 AC: 122181 AN: 152194 Hom.: 49131 Cov.: 34 AF XY: 0.803 AC XY: 59786 AN XY: 74408

African (AFR) AF: 0.795 AC: 33038 AN: 41552

American (AMR) AF: 0.810 AC: 12401 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2727 AN: 3472

East Asian (EAS) AF: 0.794 AC: 4075 AN: 5134

South Asian (SAS) AF: 0.752 AC: 3632 AN: 4828

European-Finnish (FIN) AF: 0.835 AC: 8856 AN: 10606

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.805 AC: 54704 AN: 67978

Other (OTH) AF: 0.810 AC: 1713 AN: 2114

Alfa AF: 0.797 Hom.: 21431

Bravo AF: 0.801

Asia WGS AF: 0.750 AC: 2610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.79
PhyloP100		-0.052
PromoterAI		0.085	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1187323; hg19: chr9-87283416;