dbSNP rs35355998: ESRP2:p.Ala691Pro (chr16-68230309-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_024939.3(ESRP2):c.2071G>C(p.Ala691Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A691T) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ESRP2
NM_024939.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.03

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04535705).

BP6

Variant 16-68230309-C-G is Benign according to our data. Variant chr16-68230309-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3090562.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 18 AD gene.

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.2071G>C	p.Ala691Pro	missense	Exon 15 of 15	NP_079215.2
ESRP2	NM_001365264.1		c.2101G>C	p.Ala701Pro	missense	Exon 15 of 15	NP_001352193.1	Q9H6T0-1
ESRP2	NM_001365265.1		c.1905G>C	p.Pro635Pro	synonymous	Exon 14 of 14	NP_001352194.1	A0A0A1TE42

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ESRP2	ENST00000473183.7	TSL:1 MANE Select	c.2071G>C	p.Ala691Pro	missense	Exon 15 of 15	ENSP00000418748.2	Q9H6T0-2
ESRP2	ENST00000251366.7	TSL:1	n.2036G>C		non_coding_transcript_exon	Exon 13 of 13
ESRP2	ENST00000889115.1		c.2176G>C	p.Ala726Pro	missense	Exon 16 of 16	ENSP00000559174.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251452

AF XY:

0.0000294

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1112000

Other (OTH)

AF:

0.0000166

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.060

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.0076

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.58

M_CAP

Benign

0.0068

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.2

PhyloP100

3.0

PrimateAI

Uncertain

0.48

PROVEAN

Benign

1.1

REVEL

Benign

0.064

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.062

MutPred

0.50

Gain of catalytic residue at P700 (P = 0.0133)

MVP

0.043

MPC

0.39

ClinPred

0.0059

GERP RS

3.7

Varity_R

0.072

gMVP

0.43

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over