7-158856643-C-T

Position:

• chr7-158856643-C-T

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.-93C>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 0.00447 in 1,205,286 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (122 hom., cov: 34)
  • Exomes 𝑓: 0.0020 (56 hom.)
• Consequence: DYNC2I1 NM_018051.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0810

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=-0.96).
• BP6: Variant 7-158856643-C-T is Benign according to our data. Variant chr7-158856643-C-T is described in ClinVar as [Benign]. Clinvar id is 1271509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC2I1	NM_018051.5	c.-93C>T		5_prime_UTR_variant	1/25	ENST00000407559.8	NP_060521.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2I1	ENST00000407559.8	c.-93C>T		5_prime_UTR_variant	1/25	1	NM_018051.5	ENSP00000384290	P1

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3222 AN: 152212 Hom.: 119 Cov.: 34

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00968

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.00204 AC: 2146 AN: 1052956 Hom.: 56 Cov.: 18 AF XY: 0.00191 AC XY: 952 AN XY: 498404

Gnomad4 AFR exome AF: 0.0731

Gnomad4 AMR exome AF: 0.00710

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000228

Gnomad4 SAS exome AF: 0.000529

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000221

Gnomad4 OTH exome AF: 0.00532

GnomAD4 genome AF: 0.0213 AC: 3241 AN: 152330 Hom.: 122 Cov.: 34 AF XY: 0.0205 AC XY: 1529 AN XY: 74488

Gnomad4 AFR AF: 0.0733

Gnomad4 AMR AF: 0.00967

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.000717 Hom.: 0

Bravo AF: 0.0236

Asia WGS AF: 0.00722 AC: 25 AN: 3478

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	May 26, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.9
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs113559273; hg19: chr7-158649334;