7-158870007-T-C

Position:

• chr7-158870007-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.69+99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,014,496 control chromosomes in the GnomAD database, including 77,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15407 hom., cov: 32)
  • Exomes 𝑓: 0.37 (62059 hom.)
• Consequence: DYNC2I1 NM_018051.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.28

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=-0.9).
• BP6: Variant 7-158870007-T-C is Benign according to our data. Variant chr7-158870007-T-C is described in ClinVar as [Benign]. Clinvar id is 1252687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC2I1	NM_018051.5	c.69+99T>C		intron_variant		ENST00000407559.8	NP_060521.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2I1	ENST00000407559.8	c.69+99T>C		intron_variant		1	NM_018051.5	ENSP00000384290	P1
DYNC2I1	ENST00000397143.3	c.-70+99T>C		intron_variant		3		ENSP00000380330

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65884 AN: 151858 Hom.: 15380 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.410

GnomAD4 exome AF: 0.372 AC: 320668 AN: 862518 Hom.: 62059 AF XY: 0.373 AC XY: 165080 AN XY: 442536

Gnomad4 AFR exome AF: 0.604

Gnomad4 AMR exome AF: 0.362

Gnomad4 ASJ exome AF: 0.342

Gnomad4 EAS exome AF: 0.672

Gnomad4 SAS exome AF: 0.460

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.377

GnomAD4 genome AF: 0.434 AC: 65958 AN: 151978 Hom.: 15407 Cov.: 32 AF XY: 0.438 AC XY: 32560 AN XY: 74276

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.409

Alfa AF: 0.211 Hom.: 371

Bravo AF: 0.441

Asia WGS AF: 0.544 AC: 1891 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	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
DANN	Benign	0.44

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: rs842696; hg19: chr7-158662698; COSMIC: COSV68107436;