rs1020577761

Variant names:

• chr2-70833778-C-T
• rs1020577761
• NM_015717.5:c.433G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015717.5(CD207):​c.433G>A​(p.Glu145Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CD207 NM_015717.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.423

Genes affected

CD207 (HGNC:17935): (CD207 molecule) The protein encoded by this gene is expressed only in Langerhans cells which are immature dendritic cells of the epidermis and mucosa. It is localized in the Birbeck granules, organelles present in the cytoplasm of Langerhans cells and consisting of superimposed and zippered membranes. It is a C-type lectin with mannose binding specificity, and it has been proposed that mannose binding by this protein leads to internalization of antigen into Birbeck granules and providing access to a nonclassical antigen-processing pathway. Mutations in this gene result in Birbeck granules deficiency or loss of sugar binding activity. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092296004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD207	NM_015717.5	c.433G>A	p.Glu145Lys	missense_variant	Exon 3 of 6	ENST00000410009.5	NP_056532.4
CD207	XM_011532875.3	c.433G>A	p.Glu145Lys	missense_variant	Exon 3 of 7		XP_011531177.1
CD207	XM_011532876.3	c.433G>A	p.Glu145Lys	missense_variant	Exon 3 of 6		XP_011531178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD207	ENST00000410009.5	c.433G>A	p.Glu145Lys	missense_variant	Exon 3 of 6	1	NM_015717.5	ENSP00000386378.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461706 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727136

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.433G>A (p.E145K) alteration is located in exon 3 (coding exon 3) of the CD207 gene. This alteration results from a G to A substitution at nucleotide position 433, causing the glutamic acid (E) at amino acid position 145 to be replaced by a lysine (K). 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	Benign	0.071
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Benign	0.81
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.035
Sift	Benign	0.20	T
Sift4G	Benign	0.17	T
Polyphen		0.0020	B
Vest4		0.17
MutPred		0.45		Gain of MoRF binding (P = 0.0016);
MVP		0.35
MPC		0.18
ClinPred		0.049	T
GERP RS		-0.78
Varity_R		0.044
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1020577761; hg19: chr2-71060909;