2-70833805-G-C

Position:

• chr2-70833805-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_015717.5(CD207):​c.406C>G​(p.Gln136Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,613,668 control chromosomes in the GnomAD database, including 70,186 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.22 (4608 hom., cov: 32)
  • Exomes 𝑓: 0.29 (65578 hom.)
• Consequence: CD207 NM_015717.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.846

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0046016574).
• BP6: Variant 2-70833805-G-C is Benign according to our data. Variant chr2-70833805-G-C is described in ClinVar as [Benign]. Clinvar id is 3060755.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD207	NM_015717.5	c.406C>G	p.Gln136Glu	missense_variant	3/6	ENST00000410009.5	NP_056532.4
CD207	XM_011532875.3	c.406C>G	p.Gln136Glu	missense_variant	3/7		XP_011531177.1
CD207	XM_011532876.3	c.406C>G	p.Gln136Glu	missense_variant	3/6		XP_011531178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD207	ENST00000410009.5	c.406C>G	p.Gln136Glu	missense_variant	3/6	1	NM_015717.5	ENSP00000386378	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33159 AN: 152044 Hom.: 4612 Cov.: 32

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.236

GnomAD3 exomes AF: 0.232 AC: 57899 AN: 249198 Hom.: 8211 AF XY: 0.242 AC XY: 32664 AN XY: 135184

Gnomad AFR exome AF: 0.0619

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.312

Gnomad EAS exome AF: 0.00134

Gnomad SAS exome AF: 0.210

Gnomad FIN exome AF: 0.253

Gnomad NFE exome AF: 0.317

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.289 AC: 422534 AN: 1461506 Hom.: 65578 Cov.: 40 AF XY: 0.288 AC XY: 209257 AN XY: 727040

Gnomad4 AFR exome AF: 0.0625

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.314

Gnomad4 EAS exome AF: 0.00101

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.218 AC: 33159 AN: 152162 Hom.: 4608 Cov.: 32 AF XY: 0.214 AC XY: 15919 AN XY: 74376

Gnomad4 AFR AF: 0.0690

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.233

Alfa AF: 0.294 Hom.: 2274

Bravo AF: 0.204

TwinsUK AF: 0.327 AC: 1214

ALSPAC AF: 0.315 AC: 1213

ESP6500AA AF: 0.0729 AC: 285

ESP6500EA AF: 0.306 AC: 2538

ExAC AF: 0.233 AC: 28149

Asia WGS AF: 0.112 AC: 390 AN: 3478

EpiCase AF: 0.320

EpiControl AF: 0.320

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CD207-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.16
DEOGEN2	Benign	0.062	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.055
Sift	Benign	0.46	T
Sift4G	Benign	0.091	T
Polyphen		0.010	B
Vest4		0.030
MPC		0.15
ClinPred		0.0031	T
GERP RS		0.19
Varity_R		0.042
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17718987; hg19: chr2-71060936; COSMIC: COSV69652062;