8-94372264-T-C

Position:

• chr8-94372264-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_012415.3(RAD54B):​c.2639A>G​(p.Asp880Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,613,124 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (18 hom.)
• Consequence: RAD54B NM_012415.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.58

Genes affected

RAD54B (HGNC:17228): (RAD54 homolog B) The protein encoded by this gene belongs to the DEAD-like helicase superfamily. It shares similarity with Saccharomyces cerevisiae RAD54 and RDH54, both of which are involved in homologous recombination and repair of DNA. This protein binds to double-stranded DNA, and displays ATPase activity in the presence of DNA. This gene is highly expressed in testis and spleen, which suggests active roles in meiotic and mitotic recombination. Homozygous mutations of this gene were observed in primary lymphoma and colon cancer. [provided by RefSeq, Jul 2008]

RAD54B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062393844).
• BP6: Variant 8-94372264-T-C is Benign according to our data. Variant chr8-94372264-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 774245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD54B	NM_012415.3	c.2639A>G	p.Asp880Gly	missense_variant	15/15	ENST00000336148.10	NP_036547.1
RAD54B	NM_001205263.2	c.2087A>G	p.Asp696Gly	missense_variant	13/13		NP_001192192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD54B	ENST00000336148.10	c.2639A>G	p.Asp880Gly	missense_variant	15/15	1	NM_012415.3	ENSP00000336606.5
RAD54B	ENST00000519348.1	n.203A>G		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes AF: 0.00223 AC: 339 AN: 152160 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00335

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00254 AC: 636 AN: 250356 Hom.: 5 AF XY: 0.00269 AC XY: 364 AN XY: 135340

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.00111

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00437

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.00347

Gnomad OTH exome AF: 0.00327

GnomAD4 exome AF: 0.00303 AC: 4421 AN: 1460846 Hom.: 18 Cov.: 31 AF XY: 0.00305 AC XY: 2213 AN XY: 726726

Gnomad4 AFR exome AF: 0.000718

Gnomad4 AMR exome AF: 0.00126

Gnomad4 ASJ exome AF: 0.00161

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00441

Gnomad4 FIN exome AF: 0.00163

Gnomad4 NFE exome AF: 0.00321

Gnomad4 OTH exome AF: 0.00297

GnomAD4 genome AF: 0.00223 AC: 339 AN: 152278 Hom.: 1 Cov.: 33 AF XY: 0.00224 AC XY: 167 AN XY: 74454

Gnomad4 AFR AF: 0.000794

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00335

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00288 Hom.: 0

Bravo AF: 0.00205

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00279 AC: 24

ExAC AF: 0.00255 AC: 310

Asia WGS AF: 0.00289 AC: 10 AN: 3476

EpiCase AF: 0.00327

EpiControl AF: 0.00302

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 29, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.0062	T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.0	N;.
REVEL	Benign	0.22
Sift	Benign	0.22	T;.
Sift4G	Benign	0.19	T;T
Polyphen		0.0070	B;.
Vest4		0.15
MVP		0.85
MPC		0.11
ClinPred		0.021	T
GERP RS		4.5
Varity_R		0.11
gMVP		0.37

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: rs116312454; hg19: chr8-95384492;