3-196295879-T-C

Position:

• chr3-196295879-T-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.381+127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 786,918 control chromosomes in the GnomAD database, including 54,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8897 hom., cov: 33)
  • Exomes 𝑓: 0.36 (45346 hom.)
• Consequence: DYNLT2B NM_152773.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0520

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]

ENSG00000272741 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-196295879-T-C is Benign according to our data. Variant chr3-196295879-T-C is described in ClinVar as [Benign]. Clinvar id is 1254987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNLT2B	NM_152773.5	c.381+127A>G		intron_variant		ENST00000325318.10	NP_689986.2
DYNLT2B	NM_001351628.2	c.381+127A>G		intron_variant			NP_001338557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNLT2B	ENST00000325318.10	c.381+127A>G		intron_variant		1	NM_152773.5	ENSP00000324323.5
ENSG00000272741	ENST00000431391.1	n.317+11064A>G		intron_variant		5		ENSP00000405181.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48616 AN: 151982 Hom.: 8879 Cov.: 33

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.356 AC: 225838 AN: 634818 Hom.: 45346 AF XY: 0.359 AC XY: 117398 AN XY: 327316

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.454

Gnomad4 ASJ exome AF: 0.371

Gnomad4 EAS exome AF: 0.842

Gnomad4 SAS exome AF: 0.436

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.320 AC: 48661 AN: 152100 Hom.: 8897 Cov.: 33 AF XY: 0.327 AC XY: 24280 AN XY: 74342

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.334

Alfa AF: 0.307 Hom.: 1195

Bravo AF: 0.329

Asia WGS AF: 0.592 AC: 2057 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
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	-0.84
CADD	Benign	1.4
DANN	Benign	0.78

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: rs2293160; hg19: chr3-196022750;