7-158856682-A-G

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.-54A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,231,196 control chromosomes in the GnomAD database, including 83,137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (14552 hom., cov: 34)
  • Exomes 𝑓: 0.35 (68585 hom.)
• Consequence: DYNC2I1 NM_018051.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.246

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 7-158856682-A-G is Benign according to our data. Variant chr7-158856682-A-G is described in ClinVar as [Benign]. Clinvar id is 1263568.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2I1	NM_018051.5	c.-54A>G		5_prime_UTR_variant	1/25	ENST00000407559.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2I1	ENST00000407559.8	c.-54A>G		5_prime_UTR_variant	1/25	1	NM_018051.5	P1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64387 AN: 151922 Hom.: 14532 Cov.: 34

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.350 AC: 377524 AN: 1079162 Hom.: 68585 Cov.: 32 AF XY: 0.349 AC XY: 177690 AN XY: 509698

Gnomad4 AFR exome AF: 0.572

Gnomad4 AMR exome AF: 0.363

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.672

Gnomad4 SAS exome AF: 0.452

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.332

Gnomad4 OTH exome AF: 0.372

GnomAD4 genome AF: 0.424 AC: 64450 AN: 152034 Hom.: 14552 Cov.: 34 AF XY: 0.428 AC XY: 31837 AN XY: 74314

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.404

Alfa AF: 0.385 Hom.: 1442

Bravo AF: 0.429

Asia WGS AF: 0.544 AC: 1883 AN: 3468

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

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	7.8
Dann	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2657385; hg19: chr7-158649373; COSMIC: COSV68107433;