chr5-69441656-G-T

Variant names:

• chr5-69441656-G-T
• rs530892254
• ENST00000413223.3:n.*2G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000325631.10(MARVELD2):​c.*2G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,401,132 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: MARVELD2 ENST00000325631.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 49

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000325631.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARVELD2	NM_001038603.3	MANE Select	c.*2G>T		3_prime_UTR	Exon 7 of 7	NP_001033692.2
	MARVELD2	NM_001244734.2		c.*2G>T		3_prime_UTR	Exon 6 of 6	NP_001231663.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARVELD2	ENST00000413223.3	TSL:1	n.*2G>T		non_coding_transcript_exon	Exon 7 of 8	ENSP00000398922.2
	MARVELD2	ENST00000325631.10	TSL:1 MANE Select	c.*2G>T		3_prime_UTR	Exon 7 of 7	ENSP00000323264.5
	MARVELD2	ENST00000454295.6	TSL:1	c.*2G>T		3_prime_UTR	Exon 6 of 6	ENSP00000396244.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1401132 Hom.: 0 Cov.: 26 AF XY: 0.00000143 AC XY: 1 AN XY: 700064

African (AFR) AF: 0.00 AC: 0 AN: 32072

American (AMR) AF: 0.00 AC: 0 AN: 44260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25576

East Asian (EAS) AF: 0.00 AC: 0 AN: 39184

South Asian (SAS) AF: 0.00 AC: 0 AN: 83460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4320

European-Non Finnish (NFE) AF: 9.42e-7 AC: 1 AN: 1061062

Other (OTH) AF: 0.00 AC: 0 AN: 58184

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.2
DANN	Benign	0.70
PhyloP100		-0.073

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

Other links and lift over

dbSNP: rs530892254; hg19: chr5-68737483;