3-196295879-T-C

Variant names:

• chr3-196295879-T-C
• rs2293160
• NM_152773.5:c.381+127A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

DYNLT2B Gene-Disease associations (from GenCC):

• short-rib thoracic dysplasia 17 with or without polydactyly

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ENSG00000272741 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152773.5. 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
	DYNLT2B	NM_152773.5	MANE Select	c.381+127A>G		intron	N/A	NP_689986.2	Q8WW35
	DYNLT2B	NM_001351628.2		c.381+127A>G		intron	N/A	NP_001338557.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLT2B	ENST00000325318.10	TSL:1 MANE Select	c.381+127A>G		intron	N/A	ENSP00000324323.5	Q8WW35
	ENSG00000272741	ENST00000431391.1	TSL:5	n.317+11064A>G		intron	N/A	ENSP00000405181.1	E7ESA3
	DYNLT2B	ENST00000931284.1		c.555+127A>G		intron	N/A	ENSP00000601343.1

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

African (AFR) AF: 0.223 AC: 3566 AN: 15974

American (AMR) AF: 0.454 AC: 9241 AN: 20358

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 5660 AN: 15258

East Asian (EAS) AF: 0.842 AC: 27727 AN: 32928

South Asian (SAS) AF: 0.436 AC: 20213 AN: 46396

European-Finnish (FIN) AF: 0.271 AC: 12438 AN: 45916

Middle Eastern (MID) AF: 0.335 AC: 1293 AN: 3860

European-Non Finnish (NFE) AF: 0.318 AC: 134409 AN: 422328

Other (OTH) AF: 0.355 AC: 11291 AN: 31800

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

African (AFR) AF: 0.220 AC: 9122 AN: 41478

American (AMR) AF: 0.418 AC: 6384 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1263 AN: 3466

East Asian (EAS) AF: 0.827 AC: 4286 AN: 5184

South Asian (SAS) AF: 0.462 AC: 2229 AN: 4822

European-Finnish (FIN) AF: 0.265 AC: 2802 AN: 10584

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21613 AN: 67986

Other (OTH) AF: 0.334 AC: 704 AN: 2106

Alfa AF: 0.305 Hom.: 1215

Bravo AF: 0.329

Asia WGS AF: 0.592 AC: 2057 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.78
PhyloP100		-0.052
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2293160; hg19: chr3-196022750;