7-158932098-G-C

Position:

• chr7-158932098-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018051.5(DYNC2I1):​c.2546+1583G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,032 control chromosomes in the GnomAD database, including 34,006 homozygotes. 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: 𝑓 0.67 (34006 hom., cov: 32)
• Consequence: DYNC2I1 NM_018051.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2I1	NM_018051.5	c.2546+1583G>C		intron_variant		ENST00000407559.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2I1	ENST00000407559.8	c.2546+1583G>C		intron_variant		1	NM_018051.5	P1
DYNC2I1	ENST00000444851.5	c.*135+1583G>C		intron_variant, NMD_transcript_variant		1
DYNC2I1	ENST00000467220.1	n.4345+1583G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101091 AN: 151914 Hom.: 33970 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.661

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.666 AC: 101179 AN: 152032 Hom.: 34006 Cov.: 32 AF XY: 0.664 AC XY: 49321 AN XY: 74318

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.663

Alfa AF: 0.592 Hom.: 1757

Bravo AF: 0.661

Asia WGS AF: 0.583 AC: 2027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.36
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs2730245; hg19: chr7-158724789;