Genetic Variant MYD88:c.-8C>A (chr3-38138693-C-A) – 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.-8C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000692 in 1,444,670 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: not found (cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

MYD88
NM_002468.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.69

Publications

0 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:

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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=0.042042524).

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.-8C>A	5_prime_UTR	Exon 1 of 5	NP_002459.3	Q99836-1
MYD88	NM_001172567.2		c.-8C>A	5_prime_UTR	Exon 1 of 5	NP_001166038.2	Q99836-6
MYD88	NM_001172568.2		c.-8C>A	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.-8C>A	5_prime_UTR	Exon 1 of 5	ENSP00000498360.2	Q99836-1
MYD88	ENST00000421516.3	TSL:1	c.-8C>A	5_prime_UTR	Exon 1 of 5	ENSP00000391753.3	Q99836-6
MYD88	ENST00000417037.8	TSL:1	c.-8C>A	5_prime_UTR	Exon 1 of 4	ENSP00000401399.4	Q99836-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000692

AC:

AN:

1444670

Hom.:

Cov.:

AF XY:

0.00000837

AC XY:

AN XY:

716530

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33142

American (AMR)

AF:

0.00

AC:

AN:

44184

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25570

East Asian (EAS)

AF:

0.00

AC:

AN:

39378

South Asian (SAS)

AF:

0.00

AC:

AN:

85436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49720

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5634

European-Non Finnish (NFE)

AF:

0.00000907

AC:

AN:

1102058

Other (OTH)

AF:

0.00

AC:

AN:

59548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.29

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.014

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.30

M_CAP

Benign

0.0017

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.95

PhyloP100

-2.7

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.11

REVEL

Benign

0.016

Sift

Benign

0.57

Sift4G

Benign

0.77

Vest4

0.16

MutPred

0.18

Loss of glycosylation at P11 (P = 0.0173)

MVP

0.18

MPC

0.47

ClinPred

0.049

GERP RS

-4.9

PromoterAI

-0.13

Neutral

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over