17-40555102-G-T

Position:

• chr17-40555102-G-T

Variant summary

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

The NM_001838.4(CCR7):​c.777C>A​(p.Asn259Lys) variant causes a missense 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCR7 NM_001838.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79

Genes affected

CCR7 (HGNC:1608): (C-C motif chemokine receptor 7) The protein encoded by this gene is a member of the G protein-coupled receptor family. This receptor was identified as a gene induced by the Epstein-Barr virus (EBV), and is thought to be a mediator of EBV effects on B lymphocytes. This receptor is expressed in various lymphoid tissues and activates B and T lymphocytes. It has been shown to control the migration of memory T cells to inflamed tissues, as well as stimulate dendritic cell maturation. The chemokine (C-C motif) ligand 19 (CCL19/ECL) has been reported to be a specific ligand of this receptor. Signals mediated by this receptor regulate T cell homeostasis in lymph nodes, and may also function in the activation and polarization of T cells, and in chronic inflammation pathogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR7	NM_001838.4	c.777C>A	p.Asn259Lys	missense_variant	3/3	ENST00000246657.2	NP_001829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR7	ENST00000246657.2	c.777C>A	p.Asn259Lys	missense_variant	3/3	1	NM_001838.4	ENSP00000246657.2
CCR7	ENST00000579344.1	c.759C>A	p.Asn253Lys	missense_variant	3/3	1		ENSP00000462631.1
CCR7	ENST00000578085.1	c.588C>A	p.Asn196Lys	missense_variant	2/2	3		ENSP00000463075.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2022

The c.777C>A (p.N259K) alteration is located in exon 3 (coding exon 3) of the CCR7 gene. This alteration results from a C to A substitution at nucleotide position 777, causing the asparagine (N) at amino acid position 259 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;.;.
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.92	L;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.7	D;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.0070	D;.;.
Sift4G	Uncertain	0.021	D;D;.
Polyphen		0.89	P;.;.
Vest4		0.56
MutPred		0.47		Gain of MoRF binding (P = 0.0346);.;.;
MVP		0.65
MPC		1.8
ClinPred		0.96	D
GERP RS		3.6
Varity_R		0.51
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-38711354;