NM_018051.5:c.2546+1583G>C

Variant names:

• chr7-158932098-G-C
• rs2730245
• NM_018051.5:c.2546+1583G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018051.5(DYNC2I1):​c.2546+1583G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,032 control chromosomes in the GnomAD database, including 34,006 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (34006 hom., cov: 32)
• Consequence: DYNC2I1 NM_018051.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730
• Publications: 16 publications found

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]

DYNC2I1 Gene-Disease associations (from GenCC):

• short-rib thoracic dysplasia 8 with or without polydactyly

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short rib-polydactyly syndrome, Verma-Naumoff type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018051.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2I1	NM_018051.5	MANE Select	c.2546+1583G>C		intron	N/A	NP_060521.4
	DYNC2I1	NM_001350914.2		c.2408+1583G>C		intron	N/A	NP_001337843.1
	DYNC2I1	NM_001350915.2		c.1973+1583G>C		intron	N/A	NP_001337844.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2I1	ENST00000407559.8	TSL:1 MANE Select	c.2546+1583G>C		intron	N/A	ENSP00000384290.3
	DYNC2I1	ENST00000444851.5	TSL:1	n.*135+1583G>C		intron	N/A	ENSP00000392608.1
	DYNC2I1	ENST00000860814.1		c.2621+1583G>C		intron	N/A	ENSP00000530873.1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101091 AN: 151914 Hom.: 33970 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.661

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.666 AC: 101179 AN: 152032 Hom.: 34006 Cov.: 32 AF XY: 0.664 AC XY: 49321 AN XY: 74318

African (AFR) AF: 0.598 AC: 24801 AN: 41450

American (AMR) AF: 0.656 AC: 10030 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2479 AN: 3470

East Asian (EAS) AF: 0.501 AC: 2591 AN: 5172

South Asian (SAS) AF: 0.618 AC: 2981 AN: 4824

European-Finnish (FIN) AF: 0.755 AC: 7982 AN: 10572

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48089 AN: 67946

Other (OTH) AF: 0.663 AC: 1399 AN: 2110

Alfa AF: 0.592 Hom.: 1757

Bravo AF: 0.661

Asia WGS AF: 0.583 AC: 2027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.36
DANN	Benign	0.37
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2730245; hg19: chr7-158724789;