Variant chr5-69432717-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001038603.3(MARVELD2):c.1331+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,612,524 control chromosomes in the GnomAD database, including 154,419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 10448 hom., cov: 31)

Exomes 𝑓: 0.44 ( 143971 hom. )

Consequence

MARVELD2
NM_001038603.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.25

Variant links:

Genes affected

MARVELD2 (HGNC:26401): (MARVEL domain containing 2) The protein encoded by this gene is a membrane protein found at the tight junctions between epithelial cells. The encoded protein helps establish epithelial barriers such as those in the organ of Corti, where these barriers are required for normal hearing. Defects in this gene are a cause of deafness autosomal recessive type 49 (DFNB49). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

MARVELD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 5-69432717-G-A is Benign according to our data. Variant chr5-69432717-G-A is described in ClinVar as [Benign]. Clinvar id is 1225860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARVELD2	NM_001038603.3 link	c.1331+42G>A		intron_variant		ENST00000325631.10	NP_001033692.2	Q8N4S9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARVELD2	ENST00000325631.10 link	c.1331+42G>A		intron_variant		1	NM_001038603.3	ENSP00000323264.5		Q8N4S9-1

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52100

AN:

151840

Hom.:

10450

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.326

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.464

Gnomad OTH

AF:

0.378

GnomAD3 exomes

AF:

0.382

AC:

95569

AN:

250460

Hom.:

19492

AF XY:

0.388

AC XY:

52591

AN XY:

135462

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.282

Gnomad ASJ exome

AF:

0.353

Gnomad EAS exome

AF:

0.418

Gnomad SAS exome

AF:

0.302

Gnomad FIN exome

AF:

0.401

Gnomad NFE exome

AF:

0.462

Gnomad OTH exome

AF:

0.399

GnomAD4 exome

AF:

0.437

AC:

637978

AN:

1460566

Hom.:

143971

Cov.:

AF XY:

0.434

AC XY:

315314

AN XY:

726654

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.286

Gnomad4 ASJ exome

AF:

0.349

Gnomad4 EAS exome

AF:

0.358

Gnomad4 SAS exome

AF:

0.303

Gnomad4 FIN exome

AF:

0.404

Gnomad4 NFE exome

AF:

0.471

Gnomad4 OTH exome

AF:

0.414

GnomAD4 genome

AF:

0.343

AC:

52095

AN:

151958

Hom.:

10448

Cov.:

AF XY:

0.337

AC XY:

25041

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.326

Gnomad4 ASJ

AF:

0.368

Gnomad4 EAS

AF:

0.402

Gnomad4 SAS

AF:

0.293

Gnomad4 FIN

AF:

0.402

Gnomad4 NFE

AF:

0.464

Gnomad4 OTH

AF:

0.375

Alfa

AF:

0.423

Hom.:

7562

Bravo

AF:

0.333

Asia WGS

AF:

0.323

AC:

1124

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.1

DANN

Benign

0.78

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