2-70831704-A-G

Variant names:

• chr2-70831704-A-G
• rs741326
• NM_015717.5:c.833T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V278E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.47 (16684 hom., cov: 32)
  • Exomes 𝑓: 0.45 (146482 hom.)
• Consequence: CD207 NM_015717.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.82
• Publications: 44 publications found

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]

CD207 Gene-Disease associations (from GenCC):

• Birbeck granule deficiency

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -13 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 VariationId is 3059640.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015717.5. 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
	CD207	NM_015717.5	MANE Select	c.833T>C	p.Val278Ala	missense	Exon 5 of 6	NP_056532.4	Q9UJ71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD207	ENST00000410009.5	TSL:1 MANE Select	c.833T>C	p.Val278Ala	missense	Exon 5 of 6	ENSP00000386378.3	Q9UJ71

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

GnomAD2 exomes AF: 0.473 AC: 117849 AN: 249170 AF XY: 0.475

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 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

African (AFR) AF: 0.470 AC: 15561 AN: 33080

American (AMR) AF: 0.468 AC: 20915 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 8812 AN: 26038

East Asian (EAS) AF: 0.690 AC: 27321 AN: 39582

South Asian (SAS) AF: 0.554 AC: 47557 AN: 85906

European-Finnish (FIN) AF: 0.532 AC: 28410 AN: 53394

Middle Eastern (MID) AF: 0.436 AC: 2498 AN: 5734

European-Non Finnish (NFE) AF: 0.424 AC: 466025 AN: 1097828

Other (OTH) AF: 0.444 AC: 26556 AN: 59858

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

African (AFR) AF: 0.480 AC: 19906 AN: 41448

American (AMR) AF: 0.475 AC: 7249 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1171 AN: 3464

East Asian (EAS) AF: 0.659 AC: 3401 AN: 5164

South Asian (SAS) AF: 0.564 AC: 2720 AN: 4824

European-Finnish (FIN) AF: 0.541 AC: 5716 AN: 10568

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29148 AN: 67956

Other (OTH) AF: 0.457 AC: 967 AN: 2116

Alfa AF: 0.436 Hom.: 38706

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

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CD207-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-1.8
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
Mutation Taster		=98/2	polymorphism (auto)

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: rs741326; hg19: chr2-71058835; COSMIC: COSV107516665;