7-158856613-T-C

Position:

• chr7-158856613-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018051.5(DYNC2I1):​c.-123T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,031,326 control chromosomes in the GnomAD database, including 64,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10553 hom., cov: 34)
  • Exomes 𝑓: 0.35 (54042 hom.)
• Consequence: DYNC2I1 NM_018051.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.366

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 7-158856613-T-C is Benign according to our data. Variant chr7-158856613-T-C is described in ClinVar as [Benign]. Clinvar id is 1179501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2I1	NM_018051.5	c.-123T>C		5_prime_UTR_variant	1/25	ENST00000407559.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2I1	ENST00000407559.8	c.-123T>C		5_prime_UTR_variant	1/25	1	NM_018051.5	P1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56308 AN: 151508 Hom.: 10546 Cov.: 34

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.346 AC: 304366 AN: 879700 Hom.: 54042 Cov.: 12 AF XY: 0.345 AC XY: 144929 AN XY: 420118

Gnomad4 AFR exome AF: 0.407

Gnomad4 AMR exome AF: 0.345

Gnomad4 ASJ exome AF: 0.334

Gnomad4 EAS exome AF: 0.565

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.335

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.372 AC: 56350 AN: 151626 Hom.: 10553 Cov.: 34 AF XY: 0.376 AC XY: 27858 AN XY: 74154

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.379

Alfa AF: 0.355 Hom.: 1169

Bravo AF: 0.370

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	9.4
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2788472; hg19: chr7-158649304;