7-158911556-A-T

Variant names:

• chr7-158911556-A-T
• NM_018051.5:c.1467A>T
• DYNC2I1 p.Arg489Arg

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018051.5(DYNC2I1):​c.1467A>T​(p.Arg489Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: DYNC2I1 NM_018051.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1467A>T	p.Arg489Arg	synonymous	Exon 12 of 25	NP_060521.4
	DYNC2I1	NM_001350914.2		c.1329A>T	p.Arg443Arg	synonymous	Exon 12 of 25	NP_001337843.1
	DYNC2I1	NM_001350915.2		c.894A>T	p.Arg298Arg	synonymous	Exon 11 of 24	NP_001337844.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2I1	ENST00000407559.8	TSL:1 MANE Select	c.1467A>T	p.Arg489Arg	synonymous	Exon 12 of 25	ENSP00000384290.3	Q8WVS4
	DYNC2I1	ENST00000444851.5	TSL:1	n.798A>T		non_coding_transcript_exon	Exon 8 of 20	ENSP00000392608.1	H7C022
	DYNC2I1	ENST00000860814.1		c.1542A>T	p.Arg514Arg	synonymous	Exon 13 of 26	ENSP00000530873.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.9
DANN	Benign	0.69
PhyloP100		-0.063
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.25		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-158704247;