chr9-84671000-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006180.6(NTRK2):c.212+40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,590,222 control chromosomes in the GnomAD database, including 461,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 40402 hom., cov: 32)

Exomes 𝑓: 0.76 ( 420730 hom. )

Consequence

NTRK2
NM_006180.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.830

Publications

20 publications found

Variant links:

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

NTRK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-84671000-C-T is Benign according to our data. Variant chr9-84671000-C-T is described in ClinVar as Benign. ClinVar VariationId is 1276690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006180.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NTRK2	NM_006180.6	MANE Select	c.212+40C>T	intron	N/A	NP_006171.2
NTRK2	NM_001018064.3		c.212+40C>T	intron	N/A	NP_001018074.1
NTRK2	NM_001369532.1		c.212+40C>T	intron	N/A	NP_001356461.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NTRK2	ENST00000277120.8	TSL:1 MANE Select	c.212+40C>T	intron	N/A	ENSP00000277120.3
NTRK2	ENST00000323115.11	TSL:1	c.212+40C>T	intron	N/A	ENSP00000314586.5
NTRK2	ENST00000304053.11	TSL:1	c.212+40C>T	intron	N/A	ENSP00000306167.7

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110163

AN:

151942

Hom.:

40374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.611

Gnomad AMI

AF:

0.762

Gnomad AMR

AF:

0.745

Gnomad ASJ

AF:

0.769

Gnomad EAS

AF:

0.757

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.802

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.771

Gnomad OTH

AF:

0.753

GnomAD2 exomes

AF:

0.758

AC:

174012

AN:

229630

AF XY:

0.761

show subpopulations

Gnomad AFR exome

AF:

0.612

Gnomad AMR exome

AF:

0.784

Gnomad ASJ exome

AF:

0.772

Gnomad EAS exome

AF:

0.772

Gnomad FIN exome

AF:

0.796

Gnomad NFE exome

AF:

0.771

Gnomad OTH exome

AF:

0.764

GnomAD4 exome

AF:

0.764

AC:

1098708

AN:

1438162

Hom.:

420730

Cov.:

AF XY:

0.764

AC XY:

546606

AN XY:

715698

show subpopulations

African (AFR)

AF:

0.609

AC:

20276

AN:

33296

American (AMR)

AF:

0.779

AC:

34370

AN:

44106

Ashkenazi Jewish (ASJ)

AF:

0.775

AC:

20175

AN:

26040

East Asian (EAS)

AF:

0.737

AC:

29176

AN:

39598

South Asian (SAS)

AF:

0.731

AC:

62298

AN:

85226

European-Finnish (FIN)

AF:

0.791

AC:

30979

AN:

39168

Middle Eastern (MID)

AF:

0.753

AC:

4323

AN:

5738

European-Non Finnish (NFE)

AF:

0.771

AC:

851431

AN:

1104976

Other (OTH)

AF:

0.761

AC:

45680

AN:

60014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

14207

28414

42621

56828

71035

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20320

40640

60960

81280

101600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.725

AC:

110241

AN:

152060

Hom.:

40402

Cov.:

AF XY:

0.727

AC XY:

54014

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.611

AC:

25351

AN:

41474

American (AMR)

AF:

0.745

AC:

11396

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.769

AC:

2670

AN:

3470

East Asian (EAS)

AF:

0.757

AC:

3878

AN:

5124

South Asian (SAS)

AF:

0.736

AC:

3549

AN:

4822

European-Finnish (FIN)

AF:

0.802

AC:

8491

AN:

10582

Middle Eastern (MID)

AF:

0.759

AC:

223

AN:

294

European-Non Finnish (NFE)

AF:

0.771

AC:

52403

AN:

67978

Other (OTH)

AF:

0.750

AC:

1585

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1516

3032

4548

6064

7580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

840

1680

2520

3360

4200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.746

Hom.:

71507

Bravo

AF:

0.716

Asia WGS

AF:

0.716

AC:

2490

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Obesity, hyperphagia, and developmental delay

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Developmental and epileptic encephalopathy, 58

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.5

(source)

DANN

Benign

0.46

PhyloP100

-0.83

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over