Genetic Variant RAD54B:p.Asp880Gly (chr8-94372264-T-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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. 16/22 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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.58

Publications

9 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 774245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 18 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012415.3. 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
	RAD54B	NM_012415.3	MANE Select	c.2639A>G	p.Asp880Gly	missense	Exon 15 of 15	NP_036547.1	Q9Y620-1
	RAD54B	NM_001205263.2		c.2087A>G	p.Asp696Gly	missense	Exon 13 of 13	NP_001192192.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAD54B	ENST00000336148.10	TSL:1 MANE Select	c.2639A>G	p.Asp880Gly	missense	Exon 15 of 15	ENSP00000336606.5	Q9Y620-1
RAD54B	ENST00000911517.1		c.2732A>G	p.Asp911Gly	missense	Exon 16 of 16	ENSP00000581576.1
RAD54B	ENST00000911516.1		c.2630A>G	p.Asp877Gly	missense	Exon 15 of 15	ENSP00000581575.1

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

GnomAD2 exomes

AF:

0.00254

AC:

636

AN:

250356

AF XY:

0.00269

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 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

African (AFR)

AF:

0.000718

AC:

AN:

33422

American (AMR)

AF:

0.00126

AC:

AN:

44406

Ashkenazi Jewish (ASJ)

AF:

0.00161

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39622

South Asian (SAS)

AF:

0.00441

AC:

380

AN:

86108

European-Finnish (FIN)

AF:

0.00163

AC:

AN:

53318

Middle Eastern (MID)

AF:

0.0153

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00321

AC:

3565

AN:

1111730

Other (OTH)

AF:

0.00297

AC:

179

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

313

627

940

1254

1567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00223

AC:

339

AN:

152278

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

167

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.000794

AC:

AN:

41560

American (AMR)

AF:

0.00170

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3466

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.00373

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00335

AC:

228

AN:

68022

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00289

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.68

M_CAP

Benign

0.027

MetaRNN

Benign

0.0062

MetaSVM

Benign

-0.34

MutationAssessor

Benign

2.0

PhyloP100

2.6

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.0

REVEL

Benign

0.22

Sift

Benign

0.22

Sift4G

Benign

0.19

Polyphen

0.0070

Vest4

0.15

MVP

0.85

MPC

0.11

ClinPred

0.021

GERP RS

4.5

Varity_R

0.11

gMVP

0.37

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over