2-70835702-GC-GCC

Variant names:

• chr2-70835702-G-GC
• rs11450450
• NM_015717.5:c.73+1dupG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_015717.5(CD207):​c.73+1dupG variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD207 NM_015717.5 splice_donor, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.34

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 2-70835702-G-GC is Benign according to our data. Variant chr2-70835702-G-GC is described in ClinVar as [Benign]. Clinvar id is 402516.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD207	NM_015717.5	c.73+1dupG		splice_donor_variant, intron_variant	Intron 1 of 5	ENST00000410009.5	NP_056532.4
CD207	XM_011532875.3	c.73+1dupG		splice_donor_variant, intron_variant	Intron 1 of 6		XP_011531177.1
CD207	XM_011532876.3	c.73+1dupG		splice_donor_variant, intron_variant	Intron 1 of 5		XP_011531178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD207	ENST00000410009.5	c.73+1_73+2insG		splice_donor_variant, intron_variant	Intron 1 of 5	1	NM_015717.5	ENSP00000386378.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 1.00 AC: 247980 AN: 247982 Hom.: 123989 AF XY: 1.00 AC XY: 134604 AN XY: 134606

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 1.00 Hom.: 6766

Asia WGS AF: 1.00 AC: 3478 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 12245/12248=99.9% -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11450450; hg19: chr2-71062833;