5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGA

Variant names:

• chr5-141573996-T-TGGAGGAGGAGGAGGAGGAGGAGGA
• NM_005219.5:c.1830_1853dupTCCTCCTCCTCCTCCTCCTCCTCC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005219.5(DIAPH1):​c.1830_1853dupTCCTCCTCCTCCTCCTCCTCCTCC​(p.Pro611_Pro618dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,386,322 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DIAPH1 NM_005219.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13

Genes affected

DIAPH1 (HGNC:2876): (diaphanous related formin 1) This gene is a homolog of the Drosophila diaphanous gene, and has been linked to autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive low-frequency hearing loss. Actin polymerization involves proteins known to interact with diaphanous protein in Drosophila and mouse. It has therefore been speculated that this gene may have a role in the regulation of actin polymerization in hair cells of the inner ear. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH1	NM_005219.5	c.1830_1853dupTCCTCCTCCTCCTCCTCCTCCTCC	p.Pro611_Pro618dup	disruptive_inframe_insertion	Exon 16 of 28	ENST00000389054.8	NP_005210.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIAPH1	ENST00000389054.8	c.1830_1853dupTCCTCCTCCTCCTCCTCCTCCTCC	p.Pro611_Pro618dup	disruptive_inframe_insertion	Exon 16 of 28	5	NM_005219.5	ENSP00000373706.4
DIAPH1	ENST00000518047.5	c.1803_1826dupTCCTCCTCCTCCTCCTCCTCCTCC	p.Pro602_Pro609dup	disruptive_inframe_insertion	Exon 15 of 27	5		ENSP00000428268.2
DIAPH1	ENST00000647433.1	c.1830_1853dupTCCTCCTCCTCCTCCTCCTCCTCC	p.Pro611_Pro618dup	disruptive_inframe_insertion	Exon 16 of 29			ENSP00000494675.1
DIAPH1	ENST00000647330.1	n.*1057_*1080dupTCCTCCTCCTCCTCCTCCTCCTCC		downstream_gene_variant				ENSP00000494308.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1386322 Hom.: 0 Cov.: 35 AF XY: 0.00000146 AC XY: 1 AN XY: 683644

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000187

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-140953563;