rs114073208

Variant names:

• chr7-158869740-C-T
• rs114073208
• NM_018051.5:c.16-115C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_018051.5(DYNC2I1):​c.16-115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 730,332 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (51 hom., cov: 33)
  • Exomes 𝑓: 0.0089 (81 hom.)
• Consequence: DYNC2I1 NM_018051.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03
• Publications: 0 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: Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine, G2P
• Jeune syndrome

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000296853 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 7-158869740-C-T is Benign according to our data. Variant chr7-158869740-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1706664.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0184 (2799/152234) while in subpopulation AFR AF = 0.0398 (1652/41514). AF 95% confidence interval is 0.0382. There are 51 homozygotes in GnomAd4. There are 1310 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 51 AR gene

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.16-115C>T		intron	N/A	NP_060521.4
	DYNC2I1	NM_001350914.2		c.-123-115C>T		intron	N/A	NP_001337843.1
	DYNC2I1	NM_001350915.2		c.-502-115C>T		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.16-115C>T		intron	N/A	ENSP00000384290.3	Q8WVS4
	DYNC2I1	ENST00000860814.1		c.16-115C>T		intron	N/A	ENSP00000530873.1
	DYNC2I1	ENST00000961351.1		c.16-115C>T		intron	N/A	ENSP00000631410.1

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2794 AN: 152116 Hom.: 51 Cov.: 33

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00712

Gnomad OTH AF: 0.0292

GnomAD4 exome AF: 0.00891 AC: 5152 AN: 578098 Hom.: 81 AF XY: 0.00895 AC XY: 2682 AN XY: 299714

African (AFR) AF: 0.0446 AC: 639 AN: 14338

American (AMR) AF: 0.0162 AC: 321 AN: 19776

Ashkenazi Jewish (ASJ) AF: 0.0592 AC: 886 AN: 14978

East Asian (EAS) AF: 0.00 AC: 0 AN: 31238

South Asian (SAS) AF: 0.00392 AC: 176 AN: 44890

European-Finnish (FIN) AF: 0.000136 AC: 6 AN: 44142

Middle Eastern (MID) AF: 0.0467 AC: 106 AN: 2270

European-Non Finnish (NFE) AF: 0.00666 AC: 2509 AN: 376878

Other (OTH) AF: 0.0172 AC: 509 AN: 29588

GnomAD4 genome AF: 0.0184 AC: 2799 AN: 152234 Hom.: 51 Cov.: 33 AF XY: 0.0176 AC XY: 1310 AN XY: 74460

African (AFR) AF: 0.0398 AC: 1652 AN: 41514

American (AMR) AF: 0.0231 AC: 354 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0582 AC: 202 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4824

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10602

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00712 AC: 484 AN: 68012

Other (OTH) AF: 0.0289 AC: 61 AN: 2114

Alfa AF: 0.0154 Hom.: 5

Bravo AF: 0.0221

Asia WGS AF: 0.00260 AC: 10 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.0
DANN	Benign	0.80
PhyloP100		-1.0
PromoterAI		0.030	Neutral
Mutation Taster		=100/0	polymorphism

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: rs114073208; hg19: chr7-158662431;