chr18-62523490-G-T

Variant names:

• chr18-62523490-G-T
• NM_017742.6:c.66G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017742.6(ZCCHC2):​c.66G>T​(p.Glu22Asp) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZCCHC2 NM_017742.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.171
• Publications: 0 publications found

Genes affected

ZCCHC2 (HGNC:22916): (zinc finger CCHC-type containing 2) Predicted to enable nucleic acid binding activity; phosphatidylinositol binding activity; and zinc ion binding activity. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053774297).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017742.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCCHC2	NM_017742.6	MANE Select	c.66G>T	p.Glu22Asp	missense	Exon 1 of 14	NP_060212.4
	ZCCHC2	NR_126534.2		n.466G>T		non_coding_transcript_exon	Exon 1 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCCHC2	ENST00000269499.10	TSL:5 MANE Select	c.66G>T	p.Glu22Asp	missense	Exon 1 of 14	ENSP00000269499.4	Q9C0B9-1
	ZCCHC2	ENST00000963441.1		c.66G>T	p.Glu22Asp	missense	Exon 1 of 14	ENSP00000633500.1
	ZCCHC2	ENST00000585873.5	TSL:1	n.-178G>T		upstream_gene	N/A	ENSP00000468789.1	K7ESN2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 867886 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 408496

African (AFR) AF: 0.00 AC: 0 AN: 16102

American (AMR) AF: 0.00 AC: 0 AN: 2308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7484

East Asian (EAS) AF: 0.00 AC: 0 AN: 4168

South Asian (SAS) AF: 0.00 AC: 0 AN: 25210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1800

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 780050

Other (OTH) AF: 0.00 AC: 0 AN: 28660

GnomAD4 genome Cov.: 28

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.30	T
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.17
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.0090
Sift	Benign	0.26	T
Sift4G	Benign	0.55	T
Polyphen		0.059	B
Vest4		0.090
MutPred		0.078		Loss of helix (P = 0.079)
MVP		0.014
MPC		0.040
ClinPred		0.053	T
GERP RS		1.1
PromoterAI		0.011	Neutral
Varity_R		0.054
gMVP		0.14

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

Other links and lift over

hg19: chr18-60190723;