rs299075

chr5-69432717-G-Achr5-69432717-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
MARVELD2	NM_001038603.3	c.1331+42G>A		intron_variant		ENST00000325631.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARVELD2	ENST00000325631.10	c.1331+42G>A		intron_variant		1	NM_001038603.3	P1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52100 AN: 151840 Hom.: 10450 Cov.: 31

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

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.: 39 AF XY: 0.434 AC XY: 315314 AN XY: 726654

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.: 31 AF XY: 0.337 AC XY: 25041 AN XY: 74260

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

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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

Other links and lift over

dbSNP: rs299075; hg19: chr5-68728544; COSMIC: COSV57780501;