rs299093

Positions:

• chr5-69422112-A-G

Variant summary

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

The NM_001038603.3(MARVELD2):​c.1146+1581A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,810 control chromosomes in the GnomAD database, including 17,575 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 0.48 (17575 hom., cov: 31)
• Consequence: MARVELD2 NM_001038603.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARVELD2	NM_001038603.3	c.1146+1581A>G		intron_variant		ENST00000325631.10	NP_001033692.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARVELD2	ENST00000325631.10	c.1146+1581A>G		intron_variant		1	NM_001038603.3	ENSP00000323264	P1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72736 AN: 151692 Hom.: 17577 Cov.: 31

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.479 AC: 72767 AN: 151810 Hom.: 17575 Cov.: 31 AF XY: 0.487 AC XY: 36121 AN XY: 74150

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.479

Alfa AF: 0.487 Hom.: 2287

Bravo AF: 0.470

Asia WGS AF: 0.510 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.47

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: rs299093; hg19: chr5-68717939; COSMIC: COSV57779916; COSMIC: COSV57779916;