Variant 16-21204351-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001376232.1(ZP2):c.747T>C(p.Pro249Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,613,452 control chromosomes in the GnomAD database, including 69,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.29 ( 6484 hom., cov: 32)

Exomes 𝑓: 0.29 ( 62967 hom. )

Consequence

ZP2
NM_001376232.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.31

Variant links:

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]

ZP2 links:

ENSG00000262983 (HGNC:):

ENSG00000262983 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 16-21204351-A-G is Benign according to our data. Variant chr16-21204351-A-G is described in ClinVar as [Benign]. Clinvar id is 3060177.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZP2	NM_001376232.1 link	c.747T>C	p.Pro249Pro	synonymous_variant	8/19	ENST00000574091.6	NP_001363161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZP2	ENST00000574091.6 link	c.747T>C	p.Pro249Pro	synonymous_variant	8/19	1	NM_001376232.1	ENSP00000458991.2	Q05996-1
ZP2	ENST00000574002.1 link	c.747T>C	p.Pro249Pro	synonymous_variant	9/20	1		ENSP00000460971.1	Q05996-1
ZP2	ENST00000576162.5 link	n.774T>C		non_coding_transcript_exon_variant	8/9	1
ENSG00000262983	ENST00000572747.1 link	n.341-1394A>G		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.286

AC:

43529

AN:

151986

Hom.:

6465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.412

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.307

GnomAD3 exomes

AF:

0.306

AC:

76739

AN:

250884

Hom.:

12097

AF XY:

0.307

AC XY:

41652

AN XY:

135558

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.328

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.407

Gnomad SAS exome

AF:

0.365

Gnomad FIN exome

AF:

0.309

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.290

AC:

424138

AN:

1461348

Hom.:

62967

Cov.:

AF XY:

0.292

AC XY:

212056

AN XY:

726980

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.328

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.419

Gnomad4 SAS exome

AF:

0.361

Gnomad4 FIN exome

AF:

0.304

Gnomad4 NFE exome

AF:

0.280

Gnomad4 OTH exome

AF:

0.302

GnomAD4 genome

AF:

0.286

AC:

43575

AN:

152104

Hom.:

6484

Cov.:

AF XY:

0.292

AC XY:

21739

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.232

Gnomad4 AMR

AF:

0.343

Gnomad4 ASJ

AF:

0.267

Gnomad4 EAS

AF:

0.412

Gnomad4 SAS

AF:

0.375

Gnomad4 FIN

AF:

0.321

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.311

Alfa

AF:

0.275

Hom.:

4319

Bravo

AF:

0.284

Asia WGS

AF:

0.439

AC:

1523

AN:

3478

EpiCase

AF:

0.286

EpiControl

AF:

0.281

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZP2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.0

DANN

Benign

0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over