3-38138992-CGC-GGT

Variant names:

• chr3-38138992-CGC-GGT
• NM_002468.5:c.292_294delCGCinsGGT
• MYD88 p.Arg98Gly

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_002468.5(MYD88):​c.292_294delCGCinsGGT​(p.Arg98Gly) variant causes a missense change involving the alteration of a 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. Synonymous variant affecting the same amino acid position (i.e. R98R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYD88 NM_002468.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.22
• Publications: 0 publications found

Genes affected

MYD88 (HGNC:7562): (MYD88 innate immune signal transduction adaptor) This gene encodes a cytosolic adapter protein that plays a central role in the innate and adaptive immune response. This protein functions as an essential signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. These pathways regulate that activation of numerous proinflammatory genes. The encoded protein consists of an N-terminal death domain and a C-terminal Toll-interleukin1 receptor domain. Patients with defects in this gene have an increased susceptibility to pyogenic bacterial infections. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

MYD88 Gene-Disease associations (from GenCC):

• pyogenic bacterial infections due to MyD88 deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ENSG00000299092 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002468.5. 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
	MYD88	NM_002468.5	MANE Select	c.292_294delCGCinsGGT	p.Arg98Gly	missense	N/A	NP_002459.3	Q99836-1
	MYD88	NM_001172567.2		c.292_294delCGCinsGGT	p.Arg98Gly	missense	N/A	NP_001166038.2	Q99836-6
	MYD88	NM_001172568.2		c.292_294delCGCinsGGT	p.Arg98Gly	missense	N/A	NP_001166039.2	Q99836-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYD88	ENST00000650905.2	MANE Select	c.292_294delCGCinsGGT	p.Arg98Gly	missense	N/A	ENSP00000498360.2	Q99836-1
	MYD88	ENST00000421516.3	TSL:1	c.292_294delCGCinsGGT	p.Arg98Gly	missense	N/A	ENSP00000391753.3	Q99836-6
	MYD88	ENST00000417037.8	TSL:1	c.292_294delCGCinsGGT	p.Arg98Gly	missense	N/A	ENSP00000401399.4	Q99836-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.2

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: chr3-38180483;