chr2-70832906-A-G

Variant names:

• chr2-70832906-A-G
• rs6712863
• NM_015717.5:c.711T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_015717.5(CD207):​c.711T>C​(p.Ser237Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0956 in 1,612,684 control chromosomes in the GnomAD database, including 9,552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.14 (2204 hom., cov: 32)
  • Exomes 𝑓: 0.091 (7348 hom.)
• Consequence: CD207 NM_015717.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.49
• Publications: 12 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-70832906-A-G is Benign according to our data. Variant chr2-70832906-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059699.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 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.711T>C	p.Ser237Ser	synonymous	Exon 4 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.711T>C	p.Ser237Ser	synonymous	Exon 4 of 6	ENSP00000386378.3	Q9UJ71

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21237 AN: 151846 Hom.: 2197 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0959

Gnomad ASJ AF: 0.0753

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.137

GnomAD2 exomes AF: 0.0991 AC: 24629 AN: 248462 AF XY: 0.100

Gnomad AFR exome AF: 0.284

Gnomad AMR exome AF: 0.0580

Gnomad ASJ exome AF: 0.0791

Gnomad EAS exome AF: 0.118

Gnomad FIN exome AF: 0.0537

Gnomad NFE exome AF: 0.0771

Gnomad OTH exome AF: 0.0972

GnomAD4 exome AF: 0.0909 AC: 132844 AN: 1460720 Hom.: 7348 Cov.: 31 AF XY: 0.0928 AC XY: 67397 AN XY: 726620

African (AFR) AF: 0.286 AC: 9560 AN: 33454

American (AMR) AF: 0.0607 AC: 2714 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.0805 AC: 2099 AN: 26084

East Asian (EAS) AF: 0.120 AC: 4754 AN: 39682

South Asian (SAS) AF: 0.161 AC: 13881 AN: 86152

European-Finnish (FIN) AF: 0.0530 AC: 2827 AN: 53364

Middle Eastern (MID) AF: 0.141 AC: 811 AN: 5752

European-Non Finnish (NFE) AF: 0.0809 AC: 89852 AN: 1111204

Other (OTH) AF: 0.105 AC: 6346 AN: 60340

GnomAD4 genome AF: 0.140 AC: 21266 AN: 151964 Hom.: 2204 Cov.: 32 AF XY: 0.138 AC XY: 10270 AN XY: 74268

African (AFR) AF: 0.285 AC: 11813 AN: 41420

American (AMR) AF: 0.0957 AC: 1462 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0753 AC: 261 AN: 3468

East Asian (EAS) AF: 0.135 AC: 697 AN: 5172

South Asian (SAS) AF: 0.157 AC: 751 AN: 4784

European-Finnish (FIN) AF: 0.0565 AC: 597 AN: 10574

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0779 AC: 5297 AN: 67958

Other (OTH) AF: 0.136 AC: 288 AN: 2114

Alfa AF: 0.0998 Hom.: 1438

Bravo AF: 0.146

Asia WGS AF: 0.127 AC: 440 AN: 3478

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
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.53
PhyloP100		-1.5
Mutation Taster		=99/1	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: rs6712863; hg19: chr2-71060037; COSMIC: COSV69652091;