7-158869820-T-TTTTAAAC

Position:

• chr7-158869820-T-TTTTAAAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018051.5(DYNC2I1):​c.16-34_16-28dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,534,568 control chromosomes in the GnomAD database, including 110,783 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (17132 hom., cov: 0)
  • Exomes 𝑓: 0.36 (93651 hom.)
• Consequence: DYNC2I1 NM_018051.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.553

Genes affected

DYNC2I1 (HGNC:21862): (dynein 2 intermediate chain 1) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD) and may facilitate the formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes including cell cycle progression, signal transduction, apoptosis, and gene regulation. The encoded protein contains four WD repeats and may play a role in the formation of cilia. Mutations in this gene have been associated with short-rib polydactyly and Jeune syndromes. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-158869820-T-TTTTAAAC is Benign according to our data. Variant chr7-158869820-T-TTTTAAAC is described in ClinVar as [Benign]. Clinvar id is 1266963.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC2I1	NM_018051.5	c.16-34_16-28dup		intron_variant		ENST00000407559.8	NP_060521.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2I1	ENST00000407559.8	c.16-34_16-28dup		intron_variant		1	NM_018051.5	ENSP00000384290	P1
DYNC2I1	ENST00000397143.3	c.-123-34_-123-28dup		intron_variant		3		ENSP00000380330

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68457 AN: 151328 Hom.: 17091 Cov.: 0

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.451

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.427

GnomAD3 exomes AF: 0.388 AC: 85291 AN: 219840 Hom.: 17776 AF XY: 0.387 AC XY: 46376 AN XY: 119980

Gnomad AFR exome AF: 0.661

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.326

Gnomad EAS exome AF: 0.660

Gnomad SAS exome AF: 0.450

Gnomad FIN exome AF: 0.341

Gnomad NFE exome AF: 0.323

Gnomad OTH exome AF: 0.365

GnomAD4 exome AF: 0.356 AC: 492645 AN: 1383118 Hom.: 93651 Cov.: 26 AF XY: 0.358 AC XY: 247509 AN XY: 690688

Gnomad4 AFR exome AF: 0.674

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.669

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.374

GnomAD4 genome AF: 0.453 AC: 68554 AN: 151450 Hom.: 17132 Cov.: 0 AF XY: 0.457 AC XY: 33787 AN XY: 73972

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.427

Alfa AF: 0.386 Hom.: 1975

Asia WGS AF: 0.551 AC: 1916 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

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: rs3057377; hg19: chr7-158662511;