2-70835702-GC-GCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS2

The NM_015717.5(CD207):c.73+1_73+2insG variant causes a splice donor 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
• 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 Likely_benign. Variant got -4 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.
• BS2: High AC in GnomAdExome at 247980 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD207	NM_015717.5	c.73+1_73+2insG		splice_donor_variant		ENST00000410009.5
CD207	XM_011532875.3	c.73+1_73+2insG		splice_donor_variant
CD207	XM_011532876.3	c.73+1_73+2insG		splice_donor_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD207	ENST00000410009.5	c.73+1_73+2insG		splice_donor_variant		1	NM_015717.5	P1

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

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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;