rs11152349

Variant names:

• chr18-62566413-G-A
• rs11152349
• NM_017742.6:c.1846+1317G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017742.6(ZCCHC2):​c.1846+1317G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,068 control chromosomes in the GnomAD database, including 8,898 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8898 hom., cov: 32)
• Consequence: ZCCHC2 NM_017742.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZCCHC2	NM_017742.6	c.1846+1317G>A		intron_variant	Intron 11 of 13	ENST00000269499.10	NP_060212.4
ZCCHC2	NR_126534.2	n.2246+1317G>A		intron_variant	Intron 11 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZCCHC2	ENST00000269499.10	c.1846+1317G>A		intron_variant	Intron 11 of 13	5	NM_017742.6	ENSP00000269499.4
ZCCHC2	ENST00000586834.1	c.883+1317G>A		intron_variant	Intron 10 of 12	1		ENSP00000464791.1
ZCCHC2	ENST00000585873.5	n.1603+1317G>A		intron_variant	Intron 11 of 14	1		ENSP00000468789.1
ZCCHC2	ENST00000585949.1	n.588+1317G>A		intron_variant	Intron 4 of 6	2

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50399 AN: 151950 Hom.: 8913 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.352

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50391 AN: 152068 Hom.: 8898 Cov.: 32 AF XY: 0.333 AC XY: 24787 AN XY: 74324

African (AFR) AF: 0.295 AC: 12252 AN: 41472

American (AMR) AF: 0.362 AC: 5528 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1288 AN: 3470

East Asian (EAS) AF: 0.752 AC: 3889 AN: 5172

South Asian (SAS) AF: 0.426 AC: 2053 AN: 4820

European-Finnish (FIN) AF: 0.305 AC: 3226 AN: 10566

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21189 AN: 67976

Other (OTH) AF: 0.351 AC: 742 AN: 2114

Alfa AF: 0.330 Hom.: 6015

Bravo AF: 0.332

Asia WGS AF: 0.547 AC: 1900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.70
PhyloP100		-0.014
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs11152349; hg19: chr18-60233646;