2-70832906-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_015717.5(CD207):c.711T>C(p.Ser237=) 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 (★).

• Frequency:
  • Genomes: 𝑓 0.14 (2204 hom., cov: 32)
  • Exomes 𝑓: 0.091 (7348 hom.)
• Consequence: CD207 NM_015717.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49

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 -15 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 id is 3059699.Status of the report is criteria_provided_single_submitter, 1 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD207	NM_015717.5	c.711T>C	p.Ser237=	synonymous_variant	4/6	ENST00000410009.5
CD207	XM_011532875.3	c.711T>C	p.Ser237=	synonymous_variant	4/7
CD207	XM_011532876.3	c.711T>C	p.Ser237=	synonymous_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD207	ENST00000410009.5	c.711T>C	p.Ser237=	synonymous_variant	4/6	1	NM_015717.5	P1

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

GnomAD3 exomes AF: 0.0991 AC: 24629 AN: 248462 Hom.: 1701 AF XY: 0.100 AC XY: 13527 AN XY: 134788

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 SAS exome AF: 0.161

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

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.0607

Gnomad4 ASJ exome AF: 0.0805

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.0530

Gnomad4 NFE exome AF: 0.0809

Gnomad4 OTH exome AF: 0.105

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

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.0957

Gnomad4 ASJ AF: 0.0753

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0565

Gnomad4 NFE AF: 0.0779

Gnomad4 OTH AF: 0.136

Alfa AF: 0.0925 Hom.: 943

Bravo AF: 0.146

Asia WGS AF: 0.127 AC: 440 AN: 3478

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

Nov 06, 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
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.8
Dann	Benign	0.53

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: rs6712863; hg19: chr2-71060037; COSMIC: COSV69652091;