chr2-70831053-C-T

Variant names:

• chr2-70831053-C-T
• rs13421115
• NM_015717.5:c.984G>A

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.984G>A​(p.Pro328Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,611,962 control chromosomes in the GnomAD database, including 55,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.24 (4527 hom., cov: 32)
  • Exomes 𝑓: 0.26 (51445 hom.)
• Consequence: CD207 NM_015717.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.06
• Publications: 22 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=-0.81).
• BP6: Variant 2-70831053-C-T is Benign according to our data. Variant chr2-70831053-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060971.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 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.984G>A	p.Pro328Pro	synonymous	Exon 6 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.984G>A	p.Pro328Pro	synonymous	Exon 6 of 6	ENSP00000386378.3	Q9UJ71

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35802 AN: 151938 Hom.: 4522 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.244

GnomAD2 exomes AF: 0.213 AC: 52918 AN: 248124 AF XY: 0.217

Gnomad AFR exome AF: 0.215

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.00100

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.281

Gnomad OTH exome AF: 0.232

GnomAD4 exome AF: 0.257 AC: 375762 AN: 1459906 Hom.: 51445 Cov.: 31 AF XY: 0.255 AC XY: 185210 AN XY: 726162

African (AFR) AF: 0.219 AC: 7335 AN: 33440

American (AMR) AF: 0.132 AC: 5898 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 7105 AN: 26088

East Asian (EAS) AF: 0.000882 AC: 35 AN: 39692

South Asian (SAS) AF: 0.163 AC: 14012 AN: 86014

European-Finnish (FIN) AF: 0.219 AC: 11668 AN: 53380

Middle Eastern (MID) AF: 0.265 AC: 1506 AN: 5686

European-Non Finnish (NFE) AF: 0.282 AC: 313679 AN: 1110684

Other (OTH) AF: 0.241 AC: 14524 AN: 60322

GnomAD4 genome AF: 0.236 AC: 35822 AN: 152056 Hom.: 4527 Cov.: 32 AF XY: 0.230 AC XY: 17093 AN XY: 74350

African (AFR) AF: 0.215 AC: 8935 AN: 41474

American (AMR) AF: 0.191 AC: 2921 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 917 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5180

South Asian (SAS) AF: 0.151 AC: 726 AN: 4808

European-Finnish (FIN) AF: 0.210 AC: 2218 AN: 10578

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19176 AN: 67972

Other (OTH) AF: 0.241 AC: 509 AN: 2114

Alfa AF: 0.265 Hom.: 16611

Bravo AF: 0.230

Asia WGS AF: 0.103 AC: 360 AN: 3478

EpiCase AF: 0.283

EpiControl AF: 0.285

ClinVar

ClinVar submissions

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	-0.81
CADD	Benign	0.24
DANN	Benign	0.51
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13421115; hg19: chr2-71058184; COSMIC: COSV69652025;