Genetic Variant CSTF2:p.Ala242Val (chrX-100826656-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001325.3(CSTF2):c.725C>T(p.Ala242Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,096,990 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

CSTF2
NM_001325.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.57

Variant links:

Genes affected

CSTF2 (HGNC:2484): (cleavage stimulation factor subunit 2) This gene encodes a nuclear protein with an RRM (RNA recognition motif) domain. The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3' end cleavage and polyadenylation of pre-mRNAs. Specifically, this protein binds GU-rich elements within the 3'-untranslated region of mRNAs. [provided by RefSeq, Jul 2008]

CSTF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.262347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSTF2	NM_001325.3 link	c.725C>T	p.Ala242Val	missense_variant	Exon 7 of 14	ENST00000372972.7	NP_001316.1	P33240-1
CSTF2	NM_001306206.2 link	c.725C>T	p.Ala242Val	missense_variant	Exon 7 of 15		NP_001293135.1	E7EWR4B3V096B4DUD5
CSTF2	XM_047441854.1 link	c.725C>T	p.Ala242Val	missense_variant	Exon 7 of 10		XP_047297810.1
CSTF2	NM_001306209.2 link	c.703-29C>T		intron_variant	Intron 6 of 13		NP_001293138.1	P33240-2B4DUD5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CSTF2	ENST00000372972.7 link	c.725C>T	p.Ala242Val	missense_variant	Exon 7 of 14	1	NM_001325.3	ENSP00000362063.2	P33240-1
CSTF2	ENST00000415585.7 link	c.725C>T	p.Ala242Val	missense_variant	Exon 7 of 15	1		ENSP00000387996.2	E7EWR4
CSTF2	ENST00000475126.5 link	n.703-29C>T		intron_variant	Intron 6 of 13	5		ENSP00000432060.1	E9PID8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

183185

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67643

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000110

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:

0.00000182

AC:

AN:

1096990

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362492

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000568

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.725C>T (p.A242V) alteration is located in exon 7 (coding exon 7) of the CSTF2 gene. This alteration results from a C to T substitution at nucleotide position 725, causing the alanine (A) at amino acid position 242 to be replaced by a valine (V). 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

0.18

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

.;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

.;M

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.30

N;N

REVEL

Benign

0.17

Sift

Benign

0.56

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.56

P;P

Vest4

0.57

MutPred

0.28

Gain of catalytic residue at A242 (P = 0.0074);Gain of catalytic residue at A242 (P = 0.0074);

MVP

0.75

MPC

1.3

ClinPred

0.40

GERP RS

3.6

Varity_R

0.28

gMVP

0.59

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