Genetic Variant MYD88:c.-30G>C (chr3-38138671-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002468.5(MYD88):c.-30G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,561,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

MYD88
NM_002468.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Publications

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

MYD88 links:

ENSG00000299092 (HGNC:):

ENSG00000299092 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025007159).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYD88	NM_002468.5	MANE Select	c.-30G>C	5_prime_UTR	Exon 1 of 5	NP_002459.3	Q99836-1
MYD88	NM_001172567.2		c.-30G>C	5_prime_UTR	Exon 1 of 5	NP_001166038.2	Q99836-6
MYD88	NM_001172568.2		c.-30G>C	5_prime_UTR	Exon 1 of 4	NP_001166039.2	Q99836-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYD88	ENST00000650905.2	MANE Select	c.-30G>C	5_prime_UTR	Exon 1 of 5	ENSP00000498360.2	Q99836-1
MYD88	ENST00000421516.3	TSL:1	c.-30G>C	5_prime_UTR	Exon 1 of 5	ENSP00000391753.3	Q99836-6
MYD88	ENST00000417037.8	TSL:1	c.-30G>C	5_prime_UTR	Exon 1 of 4	ENSP00000401399.4	Q99836-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000383

AC:

AN:

208704

AF XY:

0.0000520

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000106

AC:

AN:

1409588

Hom.:

Cov.:

AF XY:

0.0000158

AC XY:

AN XY:

695326

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32220

American (AMR)

AF:

0.00

AC:

AN:

40558

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23684

East Asian (EAS)

AF:

0.00

AC:

AN:

38822

South Asian (SAS)

AF:

0.000160

AC:

AN:

81196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46914

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5182

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1082980

Other (OTH)

AF:

0.00

AC:

AN:

58032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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:

0.0000131

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41572

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67950

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.00

Hom.:

ExAC

AF:

0.0000252

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.6

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.017

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.79

M_CAP

Benign

0.0050

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.95

PhyloP100

-1.3

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.31

REVEL

Benign

0.0040

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.12

MutPred

0.14

Loss of glycosylation at P9 (P = 0.0548)

MVP

0.12

MPC

1.5

ClinPred

0.21

GERP RS

-4.9

PromoterAI

-0.51

Under-expression

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over