Genetic Variant ENST00000650905:c.-29A>C (chr3-38138672-A-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 ENST00000650905.2(MYD88):c.-29A>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 0.000000709 in 1,411,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

MYD88
ENST00000650905.2 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.29

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=0.05799991).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650905.2. 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.-29A>C	5_prime_UTR	Exon 1 of 5	NP_002459.3	Q99836-1
MYD88	NM_001172567.2		c.-29A>C	5_prime_UTR	Exon 1 of 5	NP_001166038.2	Q99836-6
MYD88	NM_001172568.2		c.-29A>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.-29A>C	5_prime_UTR	Exon 1 of 5	ENSP00000498360.2	Q99836-1
MYD88	ENST00000421516.3	TSL:1	c.-29A>C	5_prime_UTR	Exon 1 of 5	ENSP00000391753.3	Q99836-6
MYD88	ENST00000417037.8	TSL:1	c.-29A>C	5_prime_UTR	Exon 1 of 4	ENSP00000401399.4	Q99836-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.09e-7

AC:

AN:

1411098

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696178

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32260

American (AMR)

AF:

0.00

AC:

AN:

40732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23772

East Asian (EAS)

AF:

0.00

AC:

AN:

38884

South Asian (SAS)

AF:

0.00

AC:

AN:

81508

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5234

European-Non Finnish (NFE)

AF:

9.23e-7

AC:

AN:

1083640

Other (OTH)

AF:

0.00

AC:

AN:

58070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Pyogenic bacterial infections due to MyD88 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

2.9

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.015

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.68

M_CAP

Benign

0.0072

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.97

PhyloP100

-1.3

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.38

REVEL

Benign

0.0040

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.097

MutPred

0.11

Gain of methylation at R5 (P = 0.0449)

MVP

0.082

MPC

1.3

ClinPred

0.21

GERP RS

-2.6

PromoterAI

0.053

Neutral

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over