2-70831704-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015717.5(CD207):c.833T>C(p.Val278Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,598,148 control chromosomes in the GnomAD database, including 163,166 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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.47 (16684 hom., cov: 32)
  • Exomes 𝑓: 0.45 (146482 hom.)
• Consequence: CD207 NM_015717.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.82

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.1363623E-6).
• BP6: Variant 2-70831704-A-G is Benign according to our data. Variant chr2-70831704-A-G is described in ClinVar as [Benign]. Clinvar id is 3059640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD207	NM_015717.5	c.833T>C	p.Val278Ala	missense_variant	5/6	ENST00000410009.5
CD207	XM_011532875.3	c.833T>C	p.Val278Ala	missense_variant	5/7
CD207	XM_011532876.3	c.833T>C	p.Val278Ala	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD207	ENST00000410009.5	c.833T>C	p.Val278Ala	missense_variant	5/6	1	NM_015717.5	P1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70747 AN: 151904 Hom.: 16678 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.456

GnomAD3 exomes AF: 0.473 AC: 117849 AN: 249170 Hom.: 28706 AF XY: 0.475 AC XY: 64239 AN XY: 135172

Gnomad AFR exome AF: 0.479

Gnomad AMR exome AF: 0.467

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.637

Gnomad SAS exome AF: 0.554

Gnomad FIN exome AF: 0.534

Gnomad NFE exome AF: 0.427

Gnomad OTH exome AF: 0.454

GnomAD4 exome AF: 0.445 AC: 643655 AN: 1446126 Hom.: 146482 Cov.: 29 AF XY: 0.449 AC XY: 323193 AN XY: 720278

Gnomad4 AFR exome AF: 0.470

Gnomad4 AMR exome AF: 0.468

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.690

Gnomad4 SAS exome AF: 0.554

Gnomad4 FIN exome AF: 0.532

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.466 AC: 70789 AN: 152022 Hom.: 16684 Cov.: 32 AF XY: 0.475 AC XY: 35340 AN XY: 74328

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.457

Alfa AF: 0.432 Hom.: 27864

Bravo AF: 0.460

TwinsUK AF: 0.419 AC: 1552

ALSPAC AF: 0.445 AC: 1714

ESP6500AA AF: 0.465 AC: 1902

ESP6500EA AF: 0.424 AC: 3551

ExAC AF: 0.475 AC: 57467

EpiCase AF: 0.434

EpiControl AF: 0.432

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CD207-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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	0.053
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.0040
Dann	Benign	0.25
DEOGEN2	Benign	0.030	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.029	T
MetaRNN	Benign	0.0000041	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.56	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.74	N
REVEL	Benign	0.015
Sift	Benign	0.80	T
Sift4G	Benign	0.61	T
Polyphen		0.0	B
Vest4		0.020
MPC		0.17
ClinPred		0.022	T
GERP RS		-9.6
Varity_R		0.070
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs741326; hg19: chr2-71058835;