Genetic Variant ZSCAN2:p.Arg85Leu (chr15-84604181-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_181877.4(ZSCAN2):c.254G>T(p.Arg85Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZSCAN2
NM_181877.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

ZSCAN2 (HGNC:20994): (zinc finger and SCAN domain containing 2) The protein encoded by this gene contains several copies of zinc finger motif, which is commonly found in transcriptional regulatory proteins. Studies in mice show that this gene is expressed during embryonic development, and specifically in the testis in adult mice, suggesting that it may play a role in regulating genes in germ cells. Alternative splicing of this gene results in several transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ZSCAN2 links:

ZSCAN2-AS1 (HGNC:56673): (ZSCAN2 antisense RNA 1)

ZSCAN2-AS1 links:

LOC105370947 (HGNC:):

LOC105370947 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2681167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN2	NM_181877.4 link	c.254G>T	p.Arg85Leu	missense_variant	Exon 2 of 3	ENST00000546148.6	NP_870992.2	Q7Z7L9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN2	ENST00000546148.6 link	c.254G>T	p.Arg85Leu	missense_variant	Exon 2 of 3	2	NM_181877.4	ENSP00000445451.1		Q7Z7L9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249446

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134986

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461370

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726950

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

.;T;T;.;.;.;T;.;T

Eigen

Benign

0.12

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.85

T;.;.;T;T;T;T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.27

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;L;L;L;L;.;.;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.5

D;N;N;D;D;N;D;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0070

D;T;T;T;T;T;T;T;T

Sift4G

Uncertain

0.015

D;T;T;T;T;T;T;T;T

Polyphen

0.72, 0.98, 0.95, 0.99, 0.99

.;P;P;D;P;.;D;D;D

Vest4

0.53, 0.49, 0.50, 0.53, 0.54, 0.54, 0.51

MutPred

0.58

Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);

MVP

0.33

MPC

0.12

ClinPred

0.79

GERP RS

3.4

Varity_R

0.11

gMVP

0.48

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over