Variant 8-94372264-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.58

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD54B	NM_012415.3 linkuse as main transcript	c.2639A>G	p.Asp880Gly	missense_variant	15/15	ENST00000336148.10
RAD54B	NM_001205263.2 linkuse as main transcript	c.2087A>G	p.Asp696Gly	missense_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD54B	ENST00000336148.10 linkuse as main transcript	c.2639A>G	p.Asp880Gly	missense_variant	15/15	1	NM_012415.3	P1	Q9Y620-1
RAD54B	ENST00000519348.1 linkuse as main transcript	n.203A>G		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

339

AN:

152160

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00269

AC XY:

364

AN XY:

135340

show subpopulations

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.:

Cov.:

AF XY:

0.00305

AC XY:

2213

AN XY:

726726

show subpopulations

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.:

Cov.:

AF XY:

0.00224

AC XY:

167

AN XY:

74454

show subpopulations

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.:

Bravo

AF:

0.00205

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00255

AC:

310

Asia WGS

AF:

0.00289

AC:

AN:

3476

EpiCase

AF:

0.00327

EpiControl

AF:

0.00302

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.0062

T;T

MetaSVM

Benign

-0.34

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

0.85

PrimateAI

Benign

0.35

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

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

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