Genetic Variant ESRP2:p.Gly676Ser (chr16-68230427-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024939.3(ESRP2):c.2026G>A(p.Gly676Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,854 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ESRP2
NM_024939.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09

Publications

0 publications found

Variant links:

Genes affected

ESRP2 (HGNC:26152): (epithelial splicing regulatory protein 2) ESPR2 is an epithelial cell-type-specific splicing regulator (Warzecha et al., 2009 [PubMed 19285943]).[supplied by OMIM, Aug 2009]

ESRP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024939.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ESRP2	NM_024939.3	MANE Select	c.2026G>A	p.Gly676Ser	missense	Exon 14 of 15	NP_079215.2
ESRP2	NM_001365264.1		c.2056G>A	p.Gly686Ser	missense	Exon 14 of 15	NP_001352193.1	Q9H6T0-1
ESRP2	NM_001365265.1		c.1899-112G>A		intron	N/A	NP_001352194.1	A0A0A1TE42

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ESRP2	ENST00000473183.7	TSL:1 MANE Select	c.2026G>A	p.Gly676Ser	missense	Exon 14 of 15	ENSP00000418748.2	Q9H6T0-2
ESRP2	ENST00000251366.7	TSL:1	n.1991G>A		non_coding_transcript_exon	Exon 12 of 13
ESRP2	ENST00000889115.1		c.2131G>A	p.Gly711Ser	missense	Exon 15 of 16	ENSP00000559174.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000799

AC:

AN:

250228

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460854

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726622

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.0000448

AC:

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26032

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111368

Other (OTH)

AF:

0.00

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0053

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.4

PhyloP100

6.1

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.0

REVEL

Benign

0.27

Sift

Benign

0.051

Sift4G

Benign

0.16

Polyphen

0.99

Vest4

0.54

MutPred

0.57

Gain of relative solvent accessibility (P = 0.09)

MVP

0.52

MPC

1.0

ClinPred

0.70

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.76

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over