rs113911955

Variant names:

• chr7-158922370-TC-T
• rs113911955
• NM_018051.5:c.1922-4delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_018051.5(DYNC2I1):​c.1922-4delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,608,636 control chromosomes in the GnomAD database, including 57 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0099 (28 hom., cov: 33)
  • Exomes 𝑓: 0.00099 (29 hom.)
• Consequence: DYNC2I1 NM_018051.5 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.123
• 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: 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 -10 ACMG points.

• BP6: Variant 7-158922370-TC-T is Benign according to our data. Variant chr7-158922370-TC-T is described in ClinVar as Benign. ClinVar VariationId is 474624.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00992 (1511/152286) while in subpopulation AFR AF = 0.034 (1413/41552). AF 95% confidence interval is 0.0325. There are 28 homozygotes in GnomAd4. There are 695 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2I1	NM_018051.5	c.1922-4delC		splice_region_variant, intron_variant	Intron 15 of 24	ENST00000407559.8	NP_060521.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2I1	ENST00000407559.8	c.1922-6delC		splice_region_variant, intron_variant	Intron 15 of 24	1	NM_018051.5	ENSP00000384290.3
DYNC2I1	ENST00000444851.5	n.1253-1200delC		intron_variant	Intron 11 of 19	1		ENSP00000392608.1
DYNC2I1	ENST00000467220.1	n.3721-6delC		splice_region_variant, intron_variant	Intron 10 of 19	2

Frequencies

GnomAD3 genomes AF: 0.00994 AC: 1512 AN: 152168 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00233 AC: 572 AN: 245148 AF XY: 0.00176

Gnomad AFR exome AF: 0.0328

Gnomad AMR exome AF: 0.00131

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000449

Gnomad OTH exome AF: 0.00203

GnomAD4 exome AF: 0.000989 AC: 1440 AN: 1456350 Hom.: 29 Cov.: 30 AF XY: 0.000866 AC XY: 627 AN XY: 723922

African (AFR) AF: 0.0353 AC: 1176 AN: 33270

American (AMR) AF: 0.00172 AC: 75 AN: 43702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25852

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5734

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1109364

Other (OTH) AF: 0.00256 AC: 154 AN: 60126

GnomAD4 genome AF: 0.00992 AC: 1511 AN: 152286 Hom.: 28 Cov.: 33 AF XY: 0.00933 AC XY: 695 AN XY: 74460

African (AFR) AF: 0.0340 AC: 1413 AN: 41552

American (AMR) AF: 0.00529 AC: 81 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68020

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00610 Hom.: 4

Bravo AF: 0.0113

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Short-rib thoracic dysplasia 8 with or without polydactyly Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.12
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs113911955; hg19: chr7-158715061;