NM_018051.5:c.-147T>G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018051.5(DYNC2I1):​c.-147T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000595 in 672,352 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: DYNC2I1 NM_018051.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• 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), 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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>G		5_prime_UTR	Exon 1 of 25	NP_060521.4
	DYNC2I1	NM_001350915.2		c.-664T>G		5_prime_UTR	Exon 1 of 24	NP_001337844.1
	DYNC2I1	NM_001350917.2		c.-1513T>G		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>G		5_prime_UTR	Exon 1 of 25	ENSP00000384290.3	Q8WVS4
	DYNC2I1	ENST00000961351.1		c.-147T>G		5_prime_UTR	Exon 1 of 26	ENSP00000631410.1
	DYNC2I1	ENST00000860811.1		c.-147T>G		5_prime_UTR	Exon 1 of 25	ENSP00000530870.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000595 AC: 4 AN: 672352 Hom.: 0 Cov.: 9 AF XY: 0.00000308 AC XY: 1 AN XY: 325110

African (AFR) AF: 0.00 AC: 0 AN: 14844

American (AMR) AF: 0.00 AC: 0 AN: 7734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11606

East Asian (EAS) AF: 0.00 AC: 0 AN: 24410

South Asian (SAS) AF: 0.00 AC: 0 AN: 10916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2384

European-Non Finnish (NFE) AF: 0.00000728 AC: 4 AN: 549372

Other (OTH) AF: 0.00 AC: 0 AN: 30164

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.53
PhyloP100		-1.4
PromoterAI		0.13	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;