rs775736832

Positions:

• chr14-95099752-ACACACACACACACACACAC-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_177438.3(DICER1):​c.4206+9_4206+27del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000949 in 1,607,250 control chromosomes in the GnomAD database, including 18 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (10 hom., cov: 28)
  • Exomes 𝑓: 0.00049 (8 hom.)
• Consequence: DICER1 NM_177438.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.09

Genes affected

DICER1 (HGNC:17098): (dicer 1, ribonuclease III) This gene encodes a protein possessing an RNA helicase motif containing a DEXH box in its amino terminus and an RNA motif in the carboxy terminus. The encoded protein functions as a ribonuclease and is required by the RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression. This protein also acts as a strong antiviral agent with activity against RNA viruses, including the Zika and SARS-CoV-2 viruses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2021]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 14-95099752-ACACACACACACACACACAC-A is Benign according to our data. Variant chr14-95099752-ACACACACACACACACACAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 477189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-95099752-ACACACACACACACACACAC-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00534 (810/151568) while in subpopulation AFR AF= 0.0189 (775/41084). AF 95% confidence interval is 0.0178. There are 10 homozygotes in gnomad4. There are 389 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 810 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DICER1	NM_177438.3	c.4206+9_4206+27del		intron_variant		ENST00000343455.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DICER1	ENST00000343455.8	c.4206+9_4206+27del		intron_variant		1	NM_177438.3	P1

Frequencies

GnomAD3 genomes AF: 0.00532 AC: 806 AN: 151450 Hom.: 10 Cov.: 28

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00241

GnomAD3 exomes AF: 0.00101 AC: 231 AN: 228020 Hom.: 1 AF XY: 0.000691 AC XY: 86 AN XY: 124474

Gnomad AFR exome AF: 0.0154

Gnomad AMR exome AF: 0.000491

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000377

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000492 AC: 716 AN: 1455682 Hom.: 8 AF XY: 0.000425 AC XY: 308 AN XY: 724274

Gnomad4 AFR exome AF: 0.0174

Gnomad4 AMR exome AF: 0.000941

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000929

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.000996

GnomAD4 genome AF: 0.00534 AC: 810 AN: 151568 Hom.: 10 Cov.: 28 AF XY: 0.00525 AC XY: 389 AN XY: 74090

Gnomad4 AFR AF: 0.0189

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000589

Gnomad4 OTH AF: 0.00239

Alfa AF: 0.000336 Hom.: 0

Asia WGS AF: 0.00202 AC: 7 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Quest Diagnostics Nichols Institute San Juan Capistrano

Jun 22, 2021

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 01, 2020

See Variant Classification Assertion Criteria. -

DICER1-related tumor predisposition Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs775736832; hg19: chr14-95566089;