chr5-69437818-G-C

Variant names:

• chr5-69437818-G-C
• rs2561182
• NM_001038603.3:c.1504-2632G>C

Variant summary

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

The NM_001038603.3(MARVELD2):​c.1504-2632G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,974 control chromosomes in the GnomAD database, including 17,400 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 (17400 hom., cov: 31)
• Consequence: MARVELD2 NM_001038603.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARVELD2	NM_001038603.3	c.1504-2632G>C		intron_variant	Intron 5 of 6	ENST00000325631.10	NP_001033692.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARVELD2	ENST00000325631.10	c.1504-2632G>C		intron_variant	Intron 5 of 6	1	NM_001038603.3	ENSP00000323264.5

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72358 AN: 151854 Hom.: 17402 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.476 AC: 72388 AN: 151974 Hom.: 17400 Cov.: 31 AF XY: 0.484 AC XY: 35954 AN XY: 74280

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.472

Alfa AF: 0.477 Hom.: 2137

Bravo AF: 0.465

Asia WGS AF: 0.504 AC: 1753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.0
DANN	Benign	0.80

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: rs2561182; hg19: chr5-68733645; COSMIC: COSV57780029;