3-51662852-C-T

Variant names:

• chr3-51662852-C-T
• rs781525636
• NM_015106.4:c.3836C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015106.4(RAD54L2):​c.3836C>T​(p.Ala1279Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: RAD54L2 NM_015106.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.733
• Publications: 0 publications found

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]

TEX264 (HGNC:30247): (testis expressed 264, ER-phagy receptor) Enables signaling receptor activity. Involved in protein-DNA covalent cross-linking repair. Acts upstream of or within reticulophagy. Located in several cellular components, including autophagosome membrane; endoplasmic reticulum membrane; and replication fork. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019812167).
• BP6: Variant 3-51662852-C-T is Benign according to our data. Variant chr3-51662852-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2404420.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 19 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015106.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD54L2	NM_015106.4	MANE Select	c.3836C>T	p.Ala1279Val	missense	Exon 23 of 23	NP_055921.2	Q9Y4B4
	RAD54L2	NM_001322253.2		c.3836C>T	p.Ala1279Val	missense	Exon 24 of 24	NP_001309182.1	Q9Y4B4
	RAD54L2	NM_001322256.2		c.3836C>T	p.Ala1279Val	missense	Exon 22 of 22	NP_001309185.1	Q9Y4B4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD54L2	ENST00000684192.1	MANE Select	c.3836C>T	p.Ala1279Val	missense	Exon 23 of 23	ENSP00000507587.1	Q9Y4B4
	RAD54L2	ENST00000409535.6	TSL:5	c.3836C>T	p.Ala1279Val	missense	Exon 22 of 22	ENSP00000386520.1	Q9Y4B4
	RAD54L2	ENST00000871491.1		c.3836C>T	p.Ala1279Val	missense	Exon 22 of 22	ENSP00000541550.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000682 AC: 17 AN: 249270 AF XY: 0.0000445

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000495

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000130 AC: 19 AN: 1461048 Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6 AN XY: 726752

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.000426 AC: 19 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111706

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.080	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.020	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.73
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.34
Sift	Benign	0.17	T
Sift4G	Benign	0.20	T
Polyphen		0.0020	B
Vest4		0.027
MutPred		0.15		Gain of MoRF binding (P = 0.1211)
MVP		0.20
MPC		0.23
ClinPred		0.032	T
GERP RS		2.8
PromoterAI		-0.0072	Neutral
Varity_R		0.028
gMVP		0.30
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs781525636; hg19: chr3-51696868;