chr5-67183060-T-C

Position:

• chr5-67183060-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005582.3(CD180):​c.1783A>G​(p.Asn595Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD180 NM_005582.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33

Genes affected

CD180 (HGNC:6726): (CD180 molecule) CD180 is a cell surface molecule consisting of extracellular leucine-rich repeats (LRR) and a short cytoplasmic tail. The extracellular LRR is associated with a molecule called MD-1 and form the cell surface receptor complex, RP105/MD-1. It belongs to the family of pathogen receptors, Toll-like receptors (TLR). RP105/MD1, by working in concert with TLR4, controls B cell recognition and signaling of lipopolysaccharide (LPS), a membrane constituent of Gram-negative bacteria. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD180	NM_005582.3	c.1783A>G	p.Asn595Asp	missense_variant	3/3	ENST00000256447.5
CD180	XM_005248504.5	c.1744A>G	p.Asn582Asp	missense_variant	4/4
CD180	XM_047417178.1	c.1744A>G	p.Asn582Asp	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD180	ENST00000256447.5	c.1783A>G	p.Asn595Asp	missense_variant	3/3	1	NM_005582.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.1783A>G (p.N595D) alteration is located in exon 3 (coding exon 3) of the CD180 gene. This alteration results from a A to G substitution at nucleotide position 1783, causing the asparagine (N) at amino acid position 595 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0094	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.10
Sift	Benign	0.066	T
Sift4G	Benign	0.094	T
Polyphen		1.0	D
Vest4		0.54
MutPred		0.39		Gain of ubiquitination at K593 (P = 0.0624);
MVP		0.71
MPC		0.37
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.55
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-66478888;