Genetic Variant MYD88:n.2238A>G (chr3-38142530-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000416282.3(MYD88):n.2238A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 233,144 control chromosomes in the GnomAD database, including 3,083 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1759 hom., cov: 32)

Exomes 𝑓: 0.16 ( 1324 hom. )

Consequence

MYD88
ENST00000416282.3 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.370

Publications

72 publications found

Variant links:

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYD88	NM_002468.5 link	c.*1244A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000650905.2	NP_002459.3	Q99836-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYD88	ENST00000650905.2 link	c.*1244A>G		3_prime_UTR_variant	Exon 5 of 5		NM_002468.5	ENSP00000498360.2		Q99836-1

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20462

AN:

152036

Hom.:

1761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0457

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.0963

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.123

GnomAD4 exome

AF:

0.165

AC:

13338

AN:

80990

Hom.:

1324

Cov.:

AF XY:

0.163

AC XY:

6068

AN XY:

37220

show subpopulations

African (AFR)

AF:

0.0462

AC:

180

AN:

3896

American (AMR)

AF:

0.177

AC:

442

AN:

2500

Ashkenazi Jewish (ASJ)

AF:

0.152

AC:

779

AN:

5124

East Asian (EAS)

AF:

0.320

AC:

3654

AN:

11408

South Asian (SAS)

AF:

0.0997

AC:

AN:

702

European-Finnish (FIN)

AF:

0.194

AC:

AN:

Middle Eastern (MID)

AF:

0.0407

AC:

AN:

492

European-Non Finnish (NFE)

AF:

0.146

AC:

7312

AN:

50034

Other (OTH)

AF:

0.128

AC:

869

AN:

6772

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

634

1268

1901

2535

3169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.134

AC:

20461

AN:

152154

Hom.:

1759

Cov.:

AF XY:

0.136

AC XY:

10132

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0456

AC:

1896

AN:

41542

American (AMR)

AF:

0.188

AC:

2880

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

513

AN:

3466

East Asian (EAS)

AF:

0.352

AC:

1816

AN:

5166

South Asian (SAS)

AF:

0.0966

AC:

465

AN:

4816

European-Finnish (FIN)

AF:

0.197

AC:

2086

AN:

10568

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.154

AC:

10484

AN:

67990

Other (OTH)

AF:

0.121

AC:

256

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

890

1779

2669

3558

4448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.146

Hom.:

3065

Bravo

AF:

0.130

Asia WGS

AF:

0.174

AC:

606

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.52

(source)

DANN

Benign

0.47

PhyloP100

-0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over