Variant chr3-51629344-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_015106.4(RAD54L2):c.352C>T(p.Arg118Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000101 in 1,588,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RAD54L2
NM_015106.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.85

Variant links:

Genes affected

RAD54L2 (HGNC:29123): (RAD54 like 2) Predicted to enable ATP hydrolysis activity; protein kinase binding activity; and transcription coregulator activity. Predicted to be involved in DNA duplex unwinding. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be located in nuclear speck. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RAD54L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.40457052).

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD54L2	NM_015106.4 link	c.352C>T	p.Arg118Trp	missense_variant	Exon 5 of 23	ENST00000684192.1	NP_055921.2	Q9Y4B4B3KV54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD54L2	ENST00000684192.1 link	c.352C>T	p.Arg118Trp	missense_variant	Exon 5 of 23		NM_015106.4	ENSP00000507587.1		Q9Y4B4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000472

AC:

AN:

211976

Hom.:

AF XY:

0.00000883

AC XY:

AN XY:

113202

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000338

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:

0.0000104

AC:

AN:

1436734

Hom.:

Cov.:

AF XY:

0.00000983

AC XY:

AN XY:

712018

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000249

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:

0.0000118

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.352C>T (p.R118W) alteration is located in exon 4 (coding exon 3) of the RAD54L2 gene. This alteration results from a C to T substitution at nucleotide position 352, causing the arginine (R) at amino acid position 118 to be replaced by a tryptophan (W). 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

0.28

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.58

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.019

MetaRNN

Benign

0.40

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.25

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.021

Polyphen

1.0

Vest4

0.45

MutPred

0.40

Gain of catalytic residue at L116 (P = 0.007);

MVP

0.17

MPC

1.4

ClinPred

0.99

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.33

gMVP

0.37

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