rs11152349

chr18-62566413-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ZCCHC2	NM_017742.6	c.1846+1317G>A		intron_variant		ENST00000269499.10
ZCCHC2	NR_126534.2	n.2246+1317G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZCCHC2	ENST00000269499.10	c.1846+1317G>A		intron_variant		5	NM_017742.6	P1
ZCCHC2	ENST00000586834.1	c.883+1317G>A		intron_variant		1
ZCCHC2	ENST00000585873.5	c.1604+1317G>A		intron_variant, NMD_transcript_variant		1
ZCCHC2	ENST00000585949.1	n.588+1317G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.351

Alfa AF: 0.320 Hom.: 3710

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

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

LitVar

Other links and lift over

dbSNP: rs11152349; hg19: chr18-60233646;