NM_018051.5:c.-147T>C

Variant names:

• chr7-158856589-T-C
• rs2788473
• NM_018051.5:c.-147T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018051.5(DYNC2I1):​c.-147T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 822,394 control chromosomes in the GnomAD database, including 52,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10524 hom., cov: 34)
  • Exomes 𝑓: 0.35 (41904 hom.)
• Consequence: DYNC2I1 NM_018051.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.38
• Publications: 5 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), Laboratory for Molecular Medicine, G2P, ClinGen
• Jeune syndrome

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000296818 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-158856589-T-C is Benign according to our data. Variant chr7-158856589-T-C is described in ClinVar as Benign. ClinVar VariationId is 1179732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 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.-147T>C		5_prime_UTR	Exon 1 of 25	NP_060521.4
	DYNC2I1	NM_001350915.2		c.-664T>C		5_prime_UTR	Exon 1 of 24	NP_001337844.1
	DYNC2I1	NM_001350917.2		c.-1513T>C		5_prime_UTR	Exon 1 of 26	NP_001337846.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2I1	ENST00000407559.8	TSL:1 MANE Select	c.-147T>C		5_prime_UTR	Exon 1 of 25	ENSP00000384290.3	Q8WVS4
	DYNC2I1	ENST00000961351.1		c.-147T>C		5_prime_UTR	Exon 1 of 26	ENSP00000631410.1
	DYNC2I1	ENST00000860811.1		c.-147T>C		5_prime_UTR	Exon 1 of 25	ENSP00000530870.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56212 AN: 151860 Hom.: 10517 Cov.: 34

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.379

GnomAD4 exome AF: 0.349 AC: 233919 AN: 670416 Hom.: 41904 Cov.: 9 AF XY: 0.347 AC XY: 112660 AN XY: 324254

African (AFR) AF: 0.407 AC: 6022 AN: 14802

American (AMR) AF: 0.345 AC: 2659 AN: 7716

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 3811 AN: 11578

East Asian (EAS) AF: 0.566 AC: 13800 AN: 24378

South Asian (SAS) AF: 0.428 AC: 4647 AN: 10866

European-Finnish (FIN) AF: 0.350 AC: 7320 AN: 20916

Middle Eastern (MID) AF: 0.396 AC: 939 AN: 2372

European-Non Finnish (NFE) AF: 0.336 AC: 184098 AN: 547702

Other (OTH) AF: 0.353 AC: 10623 AN: 30086

GnomAD4 genome AF: 0.370 AC: 56255 AN: 151978 Hom.: 10524 Cov.: 34 AF XY: 0.374 AC XY: 27796 AN XY: 74288

African (AFR) AF: 0.400 AC: 16593 AN: 41488

American (AMR) AF: 0.368 AC: 5621 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1147 AN: 3462

East Asian (EAS) AF: 0.564 AC: 2889 AN: 5122

South Asian (SAS) AF: 0.441 AC: 2126 AN: 4822

European-Finnish (FIN) AF: 0.350 AC: 3705 AN: 10574

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22922 AN: 67914

Other (OTH) AF: 0.377 AC: 793 AN: 2104

Alfa AF: 0.351 Hom.: 1418

Bravo AF: 0.369

Asia WGS AF: 0.473 AC: 1644 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.0
DANN	Benign	0.62
PhyloP100		-1.4
PromoterAI		-0.046	Neutral
Mutation Taster		=300/0	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: rs2788473; hg19: chr7-158649280;