Variant 3-51627667-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015106.4(RAD54L2):c.254T>C(p.Leu85Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RAD54L2
NM_015106.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.915

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:

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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=0.07426852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD54L2	NM_015106.4 linkuse as main transcript	c.254T>C	p.Leu85Pro	missense_variant	4/23	ENST00000684192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RAD54L2	ENST00000684192.1 linkuse as main transcript	c.254T>C	p.Leu85Pro	missense_variant	4/23		NM_015106.4	P1
RAD54L2	ENST00000409535.6 linkuse as main transcript	c.254T>C	p.Leu85Pro	missense_variant	3/22	5		P1
RAD54L2	ENST00000487093.5 linkuse as main transcript	n.379T>C		non_coding_transcript_exon_variant	3/22	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457746

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724840

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 13, 2023

The c.254T>C (p.L85P) alteration is located in exon 3 (coding exon 2) of the RAD54L2 gene. This alteration results from a T to C substitution at nucleotide position 254, causing the leucine (L) at amino acid position 85 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

0.059

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.033

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.55

M_CAP

Benign

0.0058

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

1.4

REVEL

Benign

0.16

Sift

Uncertain

0.0060

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.30

MutPred

0.31

Gain of loop (P = 3e-04);

MVP

0.19

MPC

1.2

ClinPred

0.11

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.20

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over