7-158856569-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018051.5(DYNC2I1):c.-167C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 658,214 control chromosomes in the GnomAD database, including 9,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1925 hom., cov: 34)
  • Exomes 𝑓: 0.17 (8005 hom.)
• Consequence: DYNC2I1 NM_018051.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.185

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]

LOC124901796 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-158856569-C-T is Benign according to our data. Variant chr7-158856569-C-T is described in ClinVar as [Benign]. Clinvar id is 1250932.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2I1	NM_018051.5	c.-167C>T		5_prime_UTR_variant	1/25	ENST00000407559.8
LOC124901796	XR_007060627.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2I1	ENST00000407559.8	c.-167C>T		5_prime_UTR_variant	1/25	1	NM_018051.5	P1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23118 AN: 152126 Hom.: 1920 Cov.: 34

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0523

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.175 AC: 88519 AN: 505970 Hom.: 8005 Cov.: 7 AF XY: 0.174 AC XY: 43111 AN XY: 247598

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.0636

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.152 AC: 23126 AN: 152244 Hom.: 1925 Cov.: 34 AF XY: 0.151 AC XY: 11239 AN XY: 74452

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0524

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.149

Alfa AF: 0.126 Hom.: 317

Bravo AF: 0.142

Asia WGS AF: 0.107 AC: 374 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

May 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	6.4
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2657386; hg19: chr7-158649260;