3-51627673-G-T

Variant names:

• chr3-51627673-G-T
• rs565205386
• NM_015106.4:c.260G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015106.4(RAD54L2):​c.260G>T​(p.Arg87Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RAD54L2 NM_015106.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064548075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD54L2	NM_015106.4	c.260G>T	p.Arg87Leu	missense_variant	Exon 4 of 23	ENST00000684192.1	NP_055921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD54L2	ENST00000684192.1	c.260G>T	p.Arg87Leu	missense_variant	Exon 4 of 23		NM_015106.4	ENSP00000507587.1
RAD54L2	ENST00000409535.6	c.260G>T	p.Arg87Leu	missense_variant	Exon 3 of 22	5		ENSP00000386520.1
RAD54L2	ENST00000487093.5	n.385G>T		non_coding_transcript_exon_variant	Exon 3 of 22	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.6
DANN	Benign	0.97
DEOGEN2	Benign	0.080	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.021
Sift	Benign	0.042	D
Sift4G	Benign	0.31	T
Polyphen		0.0010	B
Vest4		0.24
MutPred		0.21		Gain of ubiquitination at K91 (P = 0.0185);
MVP		0.10
MPC		0.65
ClinPred		0.048	T
GERP RS		-5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.091
gMVP		0.16

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: rs565205386; hg19: chr3-51661689;