Variant 19-35270769-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003367.4(USF2):c.632A>C(p.Gln211Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,864 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

USF2
NM_003367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

Variant links:

Genes affected

USF2 (HGNC:12594): (upstream transcription factor 2, c-fos interacting) This gene encodes a member of the basic helix-loop-helix leucine zipper family of transcription factors. The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs and is involved in regulating multiple cellular processes. [provided by RefSeq, Mar 2016]

USF2 links:

USF2 (HGNC:):

USF2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20659217).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USF2	NM_003367.4 linkuse as main transcript	c.632A>C	p.Gln211Pro	missense_variant	6/10	ENST00000222305.8	NP_003358.1	Q15853-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USF2	ENST00000222305.8 linkuse as main transcript	c.632A>C	p.Gln211Pro	missense_variant	6/10	1	NM_003367.4	ENSP00000222305.2		Q15853-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251420

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

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:

0.00000616

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.632A>C (p.Q211P) alteration is located in exon 6 (coding exon 6) of the USF2 gene. This alteration results from a A to C substitution at nucleotide position 632, causing the glutamine (Q) at amino acid position 211 to be replaced by a proline (P). 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

0.086

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.33

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

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.051

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.95

D;D;D;D;D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.21

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

MetaSVM

Uncertain

0.053

MutationAssessor

Benign

1.4

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

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-2.3

N;N;.;N;.;.;.

REVEL

Benign

0.22

Sift

Benign

0.21

T;T;.;D;.;.;.

Sift4G

Benign

0.41

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

Polyphen

0.0070

B;B;B;.;B;.;.

Vest4

0.39

MutPred

0.31

.;.;.;.;Gain of glycosylation at T206 (P = 0.0513);.;.;

MVP

0.44

MPC

1.0

ClinPred

0.15

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.68

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over