5-169882855-CGA-TAG

Variant names:

• chr5-169882855-CGA-TAG
• NM_001129891.3:c.1042_1044delTCGinsCTA
• INSYN2B p.Ser348Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001129891.3(INSYN2B):​c.1042_1044delTCGinsCTA​(p.Ser348Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INSYN2B NM_001129891.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37
• Publications: 0 publications found

Genes affected

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

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INSYN2B	NM_001129891.3	MANE Select	c.1042_1044delTCGinsCTA	p.Ser348Leu	missense	N/A	NP_001123363.1	A6NMK8
	DOCK2	NM_004946.3	MANE Select	c.2799+42003_2799+42005delCGAinsTAG		intron	N/A	NP_004937.1	Q92608-1
	INSYN2B	NM_001346304.2		c.1042_1044delTCGinsCTA	p.Ser348Leu	missense	N/A	NP_001333233.1	A6NMK8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INSYN2B	ENST00000377365.4	TSL:2 MANE Select	c.1042_1044delTCGinsCTA	p.Ser348Leu	missense	N/A	ENSP00000366582.3	A6NMK8
	DOCK2	ENST00000520908.7	TSL:2 MANE Select	c.2799+42003_2799+42005delCGAinsTAG		intron	N/A	ENSP00000429283.3	Q92608-1
	DOCK2	ENST00000524185.5	TSL:1	n.2799+42003_2799+42005delCGAinsTAG		intron	N/A	ENSP00000428850.1	E5RFJ0

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-169309859;