rs2561183

Positions:

• chr5-69437871-C-A
• chr5-69437871-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001038603.3(MARVELD2):​c.1504-2579C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,912 control chromosomes in the GnomAD database, including 18,847 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (18847 hom., cov: 31)
• Consequence: MARVELD2 NM_001038603.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARVELD2	NM_001038603.3	c.1504-2579C>A		intron_variant		ENST00000325631.10	NP_001033692.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARVELD2	ENST00000325631.10	c.1504-2579C>A		intron_variant		1	NM_001038603.3	ENSP00000323264	P1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75557 AN: 151792 Hom.: 18841 Cov.: 31

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.489

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.498 AC: 75611 AN: 151912 Hom.: 18847 Cov.: 31 AF XY: 0.505 AC XY: 37466 AN XY: 74254

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.493

Alfa AF: 0.492 Hom.: 9562

Bravo AF: 0.490

Asia WGS AF: 0.511 AC: 1779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.56

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: rs2561183; hg19: chr5-68733698; COSMIC: COSV57780035;