NM_002468.5:c.-30G>C

Variant names:

• chr3-38138671-G-C
• rs541535441
• NM_002468.5:c.-30G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 1 publications found

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

ENSG00000299092 (HGNC:):

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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: 2 AN: 152132 Hom.: 0 Cov.: 33

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: 8 AN: 208704 AF XY: 0.0000520

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: 15 AN: 1409588 Hom.: 0 Cov.: 30 AF XY: 0.0000158 AC XY: 11 AN XY: 695326

African (AFR) AF: 0.00 AC: 0 AN: 32220

American (AMR) AF: 0.00 AC: 0 AN: 40558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23684

East Asian (EAS) AF: 0.00 AC: 0 AN: 38822

South Asian (SAS) AF: 0.000160 AC: 13 AN: 81196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5182

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1082980

Other (OTH) AF: 0.00 AC: 0 AN: 58032

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152250 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74460

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000252 AC: 3

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	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.6
DANN	Benign	0.44
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.95	T
PhyloP100		-1.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.0040
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.12
MutPred		0.14		Loss of glycosylation at P9 (P = 0.0548)
MVP		0.12
MPC		1.5
ClinPred		0.21	T
GERP RS		-4.9
PromoterAI		-0.51	Under-expression
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

Other links and lift over

dbSNP: rs541535441; hg19: chr3-38180162;