Variant 3-51627761-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015106.4(RAD54L2):c.341+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,613,666 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 7 hom., cov: 31)

Exomes 𝑓: 0.00060 ( 7 hom. )

Consequence

RAD54L2
NM_015106.4 splice_region, intron

Scores

Splicing: ADA: 0.00002151

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.154

Variant links:

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]

RAD54L2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-51627761-T-C is Benign according to our data. Variant chr3-51627761-T-C is described in ClinVar as [Benign]. Clinvar id is 775874.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00618 (942/152354) while in subpopulation AFR AF= 0.0213 (887/41584). AF 95% confidence interval is 0.0202. There are 7 homozygotes in gnomad4. There are 450 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 942 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD54L2	NM_015106.4 linkuse as main transcript	c.341+7T>C		splice_region_variant, intron_variant		ENST00000684192.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
RAD54L2	ENST00000684192.1 linkuse as main transcript	c.341+7T>C	splice_region_variant, intron_variant		NM_015106.4	P1
RAD54L2	ENST00000409535.6 linkuse as main transcript	c.341+7T>C	splice_region_variant, intron_variant	5		P1
RAD54L2	ENST00000487093.5 linkuse as main transcript	n.466+7T>C	splice_region_variant, intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00610

AC:

928

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00165

AC:

414

AN:

250652

Hom.:

AF XY:

0.00128

AC XY:

174

AN XY:

135466

show subpopulations

Gnomad AFR exome

AF:

0.0227

Gnomad AMR exome

AF:

0.000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000602

AC:

879

AN:

1461312

Hom.:

Cov.:

AF XY:

0.000571

AC XY:

415

AN XY:

726976

show subpopulations

Gnomad4 AFR exome

AF:

0.0211

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00618

AC:

942

AN:

152354

Hom.:

Cov.:

AF XY:

0.00604

AC XY:

450

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0213

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00316

Hom.:

Bravo

AF:

0.00750

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.7

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.050

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