17-48037713-C-G

Position:

• chr17-48037713-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_016429.4(COPZ2):​c.65G>C​(p.Gly22Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: COPZ2 NM_016429.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.277

Genes affected

COPZ2 (HGNC:19356): (COPI coat complex subunit zeta 2) This gene encodes a member of the adaptor complexes small subunit family. The encoded protein is a subunit of the coatomer protein complex, a seven-subunit complex that functions in the formation of COPI-type, non-clathrin-coated vesicles. COPI vesicles function in the retrograde Golgi-to-ER transport of dilysine-tagged proteins. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.109170735).
• BP6: Variant 17-48037713-C-G is Benign according to our data. Variant chr17-48037713-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2342371.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COPZ2	NM_016429.4	c.65G>C	p.Gly22Ala	missense_variant	1/9	ENST00000621465.5	NP_057513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COPZ2	ENST00000621465.5	c.65G>C	p.Gly22Ala	missense_variant	1/9	1	NM_016429.4	ENSP00000480707	P1
COPZ2	ENST00000580174.1	c.-100+289G>C		intron_variant		3		ENSP00000463581
COPZ2	ENST00000612370.4	n.61G>C		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.11	T
MutationTaster	Benign	1.0	D
Sift4G	Benign	0.28	T
Vest4		0.18
MVP		0.57
GERP RS		1.3
Varity_R		0.045
gMVP		0.29

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: chr17-46115078;