16-21199602-A-C

Position:

• chr16-21199602-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001376232.1(ZP2):​c.1895T>G​(p.Val632Gly) 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. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZP2 NM_001376232.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.325

Genes affected

ZP2 (HGNC:13188): (zona pellucida glycoprotein 2) The zona pellucida is an extracellular matrix that surrounds the oocyte and early embryo. It is composed of three glycoproteins with various functions during fertilization and preimplantation development. The glycosylated mature peptide is one of the structural components of the zona pellucida and functions in secondary binding and penetration of acrosome-reacted spermatozoa. Female mice lacking this gene do not form a stable zona matrix and are sterile. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ENSG00000262983 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23402753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZP2	NM_001376232.1	c.1895T>G	p.Val632Gly	missense_variant	16/19	ENST00000574091.6	NP_001363161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZP2	ENST00000574091.6	c.1895T>G	p.Val632Gly	missense_variant	16/19	1	NM_001376232.1	ENSP00000458991.2
ZP2	ENST00000574002.1	c.1895T>G	p.Val632Gly	missense_variant	17/20	1		ENSP00000460971.1
ENSG00000262983	ENST00000572747.1	n.340+1648A>C		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

May 09, 2024

The c.1895T>G (p.V632G) alteration is located in exon 16 (coding exon 16) of the ZP2 gene. This alteration results from a T to G substitution at nucleotide position 1895, causing the valine (V) at amino acid position 632 to be replaced by a glycine (G). 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	Benign	0.15
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	.;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.057	N
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Benign	0.29	T
Sift4G	Benign	0.16	T;T
Polyphen		0.63	.;P
Vest4		0.21
MutPred		0.45		.;Loss of stability (P = 0.0111);
MVP		0.84
MPC		0.11
ClinPred		0.50	D
GERP RS		-0.57
Varity_R		0.48
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-21210923;