7-158918748-C-T

Position:

• chr7-158918748-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018051.5(DYNC2I1):​c.1800C>T​(p.Ala600Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 1,613,468 control chromosomes in the GnomAD database, including 348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (22 hom., cov: 33)
  • Exomes 𝑓: 0.019 (326 hom.)
• Consequence: DYNC2I1 NM_018051.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.584

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-158918748-C-T is Benign according to our data. Variant chr7-158918748-C-T is described in ClinVar as [Benign]. Clinvar id is 474623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-158918748-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.584 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0123 (1875/152132) while in subpopulation NFE AF= 0.0213 (1448/68006). AF 95% confidence interval is 0.0204. There are 22 homozygotes in gnomad4. There are 846 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC2I1	NM_018051.5	c.1800C>T	p.Ala600Ala	synonymous_variant	15/25	ENST00000407559.8	NP_060521.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2I1	ENST00000407559.8	c.1800C>T	p.Ala600Ala	synonymous_variant	15/25	1	NM_018051.5	ENSP00000384290.3
DYNC2I1	ENST00000444851.5	n.1131C>T		non_coding_transcript_exon_variant	11/20	1		ENSP00000392608.1
DYNC2I1	ENST00000467220.1	n.3599C>T		non_coding_transcript_exon_variant	10/20	2

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1875 AN: 152014 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00360

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.00688

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00482

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.00528

GnomAD3 exomes AF: 0.0127 AC: 3163 AN: 249138 Hom.: 34 AF XY: 0.0131 AC XY: 1768 AN XY: 135188

Gnomad AFR exome AF: 0.00317

Gnomad AMR exome AF: 0.00672

Gnomad ASJ exome AF: 0.00845

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00677

Gnomad FIN exome AF: 0.00594

Gnomad NFE exome AF: 0.0212

Gnomad OTH exome AF: 0.0117

GnomAD4 exome AF: 0.0189 AC: 27578 AN: 1461336 Hom.: 326 Cov.: 31 AF XY: 0.0185 AC XY: 13477 AN XY: 726916

Gnomad4 AFR exome AF: 0.00281

Gnomad4 AMR exome AF: 0.00700

Gnomad4 ASJ exome AF: 0.00807

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00631

Gnomad4 FIN exome AF: 0.00734

Gnomad4 NFE exome AF: 0.0225

Gnomad4 OTH exome AF: 0.0156

GnomAD4 genome AF: 0.0123 AC: 1875 AN: 152132 Hom.: 22 Cov.: 33 AF XY: 0.0114 AC XY: 846 AN XY: 74372

Gnomad4 AFR AF: 0.00359

Gnomad4 AMR AF: 0.00681

Gnomad4 ASJ AF: 0.00779

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.00482

Gnomad4 NFE AF: 0.0213

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.0161 Hom.: 16

Bravo AF: 0.0122

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.17
DANN	Benign	0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs41271220; hg19: chr7-158711439;