5-169882826-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001129891.3(INSYN2B):c.1073C>T(p.Thr358Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,550,684 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

INSYN2B
NM_001129891.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.77

Publications

0 publications found

Variant links:

Genes affected

INSYN2B (HGNC:37271): (inhibitory synaptic factor family member 2B)

INSYN2B links:

DOCK2 (HGNC:2988): (dedicator of cytokinesis 2) The protein encoded by this gene belongs to the CDM protein family. It is specifically expressed in hematopoietic cells and is predominantly expressed in peripheral blood leukocytes. The protein is involved in remodeling of the actin cytoskeleton required for lymphocyte migration in response to chemokine signaling. It activates members of the Rho family of GTPases, for example RAC1 and RAC2, by acting as a guanine nucleotide exchange factor (GEF) to exchange bound GDP for free GTP. Mutations in this gene result in immunodeficiency 40 (IMD40), a combined form of immunodeficiency that affects T cell number and function, also with variable defects in B cell and NK cell function. [provided by RefSeq, May 2018]

DOCK2 Gene-Disease associations (from GenCC):

DOCK2 deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

DOCK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019827008).

BP6

Variant 5-169882826-G-A is Benign according to our data. Variant chr5-169882826-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3109992.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001129891.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INSYN2B	NM_001129891.3	MANE Select	c.1073C>T	p.Thr358Met	missense	Exon 2 of 4	NP_001123363.1	A6NMK8
DOCK2	NM_004946.3	MANE Select	c.2799+41974G>A		intron	N/A	NP_004937.1	Q92608-1
INSYN2B	NM_001346304.2		c.1073C>T	p.Thr358Met	missense	Exon 2 of 4	NP_001333233.1	A6NMK8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INSYN2B	ENST00000377365.4	TSL:2 MANE Select	c.1073C>T	p.Thr358Met	missense	Exon 2 of 4	ENSP00000366582.3	A6NMK8
DOCK2	ENST00000520908.7	TSL:2 MANE Select	c.2799+41974G>A		intron	N/A	ENSP00000429283.3	Q92608-1
DOCK2	ENST00000524185.5	TSL:1	n.2799+41974G>A		intron	N/A	ENSP00000428850.1	E5RFJ0

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

151594

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.000481

GnomAD2 exomes

AF:

0.0000510

AC:

AN:

156900

AF XY:

0.0000723

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.0000917

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000329

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000236

AC:

AN:

1398972

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

689856

show subpopulations

African (AFR)

AF:

0.000127

AC:

AN:

31586

American (AMR)

AF:

0.000112

AC:

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.0000397

AC:

AN:

25174

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35722

South Asian (SAS)

AF:

0.0000252

AC:

AN:

79226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49328

Middle Eastern (MID)

AF:

0.000527

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.0000167

AC:

AN:

1078518

Other (OTH)

AF:

0.00

AC:

AN:

58028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000119

AC:

AN:

151712

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.000194

AC:

AN:

41342

American (AMR)

AF:

0.0000657

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3464

East Asian (EAS)

AF:

0.000195

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67862

Other (OTH)

AF:

0.000476

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000868

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000387

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0010

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0042

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.25

M_CAP

Benign

0.0043

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.1

PhyloP100

-1.8

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.44

REVEL

Benign

0.076

Sift

Benign

1.0

Sift4G

Benign

0.34

Polyphen

0.012

Vest4

0.037

MutPred

0.12

Loss of relative solvent accessibility (P = 0.0071)

MVP

0.040

ClinPred

0.0085

GERP RS

-7.3

Varity_R

0.0083

gMVP

0.19

Mutation Taster

=96/4

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over