3-196318023-G-C

Position:

• chr3-196318023-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152773.5(DYNLT2B):​c.113+17C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,462,796 control chromosomes in the GnomAD database, including 84,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (8138 hom., cov: 29)
  • Exomes 𝑓: 0.33 (76068 hom.)
• Consequence: DYNLT2B NM_152773.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.78

Genes affected

DYNLT2B (HGNC:28482): (dynein light chain Tctex-type 2B) Dyneins are a group of microtubule-activated ATPases that function as molecular motors. They are divided into two subgroups of axonemal and cytoplasmic dyneins. The cytoplasmic dyneins function in intracellular motility, including retrograde axonal transport, protein sorting, organelle movement, and spindle dynamics. Molecules of conventional cytoplasmic dynein are comprised of 2 heavy chain polypeptides and a number of intermediate and light chains. This gene encodes a subunit of the human cytoplasmic dynein-2 complex. Mutations in this gene are associated with short-rib thoracic dysplasia 17 with or without polydactyly. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]

TM4SF19-DYNLT2B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-196318023-G-C is Benign according to our data. Variant chr3-196318023-G-C is described in ClinVar as [Benign]. Clinvar id is 1290749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNLT2B	NM_152773.5	c.113+17C>G		intron_variant		ENST00000325318.10
TM4SF19-DYNLT2B	NR_037950.1	n.862-1792C>G		intron_variant, non_coding_transcript_variant
DYNLT2B	NM_001351628.2	c.113+17C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNLT2B	ENST00000325318.10	c.113+17C>G		intron_variant		1	NM_152773.5	P1
DYNLT2B	ENST00000426563.5	c.117+13C>G		intron_variant, NMD_transcript_variant		2
DYNLT2B	ENST00000446494.1	c.113+17C>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45591 AN: 151282 Hom.: 8134 Cov.: 29

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.321

GnomAD3 exomes AF: 0.362 AC: 46827 AN: 129356 Hom.: 9638 AF XY: 0.360 AC XY: 25639 AN XY: 71142

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.478

Gnomad ASJ exome AF: 0.363

Gnomad EAS exome AF: 0.826

Gnomad SAS exome AF: 0.405

Gnomad FIN exome AF: 0.263

Gnomad NFE exome AF: 0.311

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.328 AC: 430191 AN: 1311404 Hom.: 76068 Cov.: 22 AF XY: 0.330 AC XY: 214097 AN XY: 648858

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.462

Gnomad4 ASJ exome AF: 0.367

Gnomad4 EAS exome AF: 0.835

Gnomad4 SAS exome AF: 0.406

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.343

GnomAD4 genome AF: 0.301 AC: 45607 AN: 151392 Hom.: 8138 Cov.: 29 AF XY: 0.308 AC XY: 22752 AN XY: 73950

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.326

Alfa AF: 0.187 Hom.: 424

Bravo AF: 0.310

Asia WGS AF: 0.574 AC: 1984 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Short-rib thoracic dysplasia 17 with or without polydactyly Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.063
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs2270769; hg19: chr3-196044894;