chr5-141515132-CCT-C

Variant names:

• chr5-141515132-CCT-C
• rs142402193
• NM_005219.5:c.*1717_*1718delAG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005219.5(DIAPH1):​c.*1717_*1718delAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000854 in 152,196 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: 𝑓 0.00084 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (0 hom.)
• Consequence: DIAPH1 NM_005219.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• Publications: 0 publications found

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]

DIAPH1 Gene-Disease associations (from GenCC):

• DIAPH1-related sensorineural hearing loss-thrombocytopenia syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• progressive microcephaly-seizures-cortical blindness-developmental delay syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
• autosomal dominant nonsyndromic hearing loss 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000301000 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005219.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIAPH1	NM_005219.5	MANE Select	c.*1717_*1718delAG		3_prime_UTR	Exon 28 of 28	NP_005210.3
	DIAPH1	NM_001079812.3		c.*1717_*1718delAG		3_prime_UTR	Exon 27 of 27	NP_001073280.1	O60610-3
	DIAPH1	NM_001314007.2		c.*1836_*1837delAG		3_prime_UTR	Exon 29 of 29	NP_001300936.1	A0A2R8Y5N1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIAPH1	ENST00000389054.8	TSL:5 MANE Select	c.*1717_*1718delAG		3_prime_UTR	Exon 28 of 28	ENSP00000373706.4	O60610-1
	DIAPH1	ENST00000647433.1		c.*1836_*1837delAG		3_prime_UTR	Exon 29 of 29	ENSP00000494675.1	A0A2R8Y5N1
	DIAPH1	ENST00000448451.6	TSL:2	c.*1717_*1718delAG		3_prime_UTR	Exon 3 of 3	ENSP00000408159.2	H7C2W8

Frequencies

GnomAD3 genomes AF: 0.000844 AC: 128 AN: 151660 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00916

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.000480

GnomAD4 exome AF: 0.00469 AC: 2 AN: 426 Hom.: 0 AF XY: 0.00391 AC XY: 1 AN XY: 256

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00478 AC: 2 AN: 418

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.000843 AC: 128 AN: 151770 Hom.: 0 Cov.: 33 AF XY: 0.00120 AC XY: 89 AN XY: 74178

African (AFR) AF: 0.000458 AC: 19 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00916 AC: 96 AN: 10480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000133 AC: 9 AN: 67852

Other (OTH) AF: 0.000476 AC: 1 AN: 2102

Alfa AF: 0.000216 Hom.: 0

Bravo AF: 0.000234

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.37
Mutation Taster		=98/2	polymorphism

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: rs142402193; hg19: chr5-140894699;