16-68230427-C-T

Variant names:

• chr16-68230427-C-T
• rs1256977216
• NM_024939.3:c.2026G>A

Variant summary

Our verdict is Uncertain significance. Variant got 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESRP2	NM_024939.3	c.2026G>A	p.Gly676Ser	missense_variant	Exon 14 of 15	ENST00000473183.7	NP_079215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESRP2	ENST00000473183.7	c.2026G>A	p.Gly676Ser	missense_variant	Exon 14 of 15	1	NM_024939.3	ENSP00000418748.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000799 AC: 2 AN: 250228 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135176

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 SAS 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: 2 AN: 1460854 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726622

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000448

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2026G>A (p.G676S) alteration is located in exon 14 (coding exon 14) of the ESRP2 gene. This alteration results from a G to A substitution at nucleotide position 2026, causing the glycine (G) at amino acid position 676 to be replaced by a serine (S). 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	0.093
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.0053	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.27
Sift	Benign	0.051	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.99	D;D
Vest4		0.54
MutPred		0.57		Gain of relative solvent accessibility (P = 0.09);.;
MVP		0.52
MPC		1.0
ClinPred		0.70	D
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

LitVar

Other links and lift over

dbSNP: rs1256977216; hg19: chr16-68264330;