dbSNP rs746651350: MYD88:c.-24_-6delGCTGAGGCTCCAGGACCGC (chr3-38138670-CGACCGCGCTGAGGCTCCAG-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP5

The NM_001172567.2(MYD88):c.-24_-6delGCTGAGGCTCCAGGACCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00055 in 1,561,362 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00058 ( 0 hom. )

Consequence

MYD88
NM_001172567.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:2O:1

Conservation

PhyloP100: 0.231

Publications

2 publications found

Variant links:

COSMIC-nc: COSV104622180

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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

MYD88 links:

ENSG00000299092 (HGNC:):

ENSG00000299092 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PP5

Variant 3-38138670-CGACCGCGCTGAGGCTCCAG-C is Pathogenic according to our data. Variant chr3-38138670-CGACCGCGCTGAGGCTCCAG-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 469578.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172567.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYD88	NM_002468.5	MANE Select	c.-24_-6delGCTGAGGCTCCAGGACCGC	5_prime_UTR	Exon 1 of 5	NP_002459.3
MYD88	NM_001172567.2		c.-24_-6delGCTGAGGCTCCAGGACCGC	5_prime_UTR	Exon 1 of 5	NP_001166038.2
MYD88	NM_001172568.2		c.-24_-6delGCTGAGGCTCCAGGACCGC	5_prime_UTR	Exon 1 of 4	NP_001166039.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYD88	ENST00000650905.2	MANE Select	c.-24_-6delGCTGAGGCTCCAGGACCGC	5_prime_UTR	Exon 1 of 5	ENSP00000498360.2
MYD88	ENST00000421516.3	TSL:1	c.-24_-6delGCTGAGGCTCCAGGACCGC	5_prime_UTR	Exon 1 of 5	ENSP00000391753.3
MYD88	ENST00000417037.8	TSL:1	c.-24_-6delGCTGAGGCTCCAGGACCGC	5_prime_UTR	Exon 1 of 4	ENSP00000401399.4

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000364

AC:

AN:

206006

AF XY:

0.000360

show subpopulations

Gnomad AFR exome

AF:

0.000153

Gnomad AMR exome

AF:

0.000328

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000640

Gnomad OTH exome

AF:

0.000603

GnomAD4 exome

AF:

0.000578

AC:

814

AN:

1409132

Hom.:

AF XY:

0.000540

AC XY:

375

AN XY:

694786

show subpopulations

African (AFR)

AF:

0.0000621

AC:

AN:

32224

American (AMR)

AF:

0.000346

AC:

AN:

40434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23466

East Asian (EAS)

AF:

0.00

AC:

AN:

38774

South Asian (SAS)

AF:

0.00

AC:

AN:

80632

European-Finnish (FIN)

AF:

0.0000429

AC:

AN:

46598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5204

European-Non Finnish (NFE)

AF:

0.000711

AC:

771

AN:

1083860

Other (OTH)

AF:

0.000431

AC:

AN:

57940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

103

154

206

257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

140

<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:

0.000296

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41458

American (AMR)

AF:

0.000131

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68042

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

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:

0.000288

Hom.:

Bravo

AF:

0.000351

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Pyogenic bacterial infections due to MyD88 deficiency (3)

MYD88-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.23

Mutation Taster

=4/196

disease causing (ClinVar)

(source)

Splicing

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

Publications

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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