3-196296090-G-T

Variant names:

• chr3-196296090-G-T
• rs75016149
• NM_152773.5:c.318-21C>A

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.318-21C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0515 in 1,608,362 control chromosomes in the GnomAD database, including 2,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (159 hom., cov: 33)
  • Exomes 𝑓: 0.053 (2285 hom.)
• Consequence: DYNLT2B NM_152773.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00700
• 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=-0.81).
• BP6: Variant 3-196296090-G-T is Benign according to our data. Variant chr3-196296090-G-T is described in ClinVar as Benign. ClinVar VariationId is 1279376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0718 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.318-21C>A		intron	N/A	NP_689986.2	Q8WW35
	DYNLT2B	NM_001351628.2		c.318-21C>A		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.318-21C>A		intron	N/A	ENSP00000324323.5	Q8WW35
	ENSG00000272741	ENST00000431391.1	TSL:5	n.317+10853C>A		intron	N/A	ENSP00000405181.1	E7ESA3
	DYNLT2B	ENST00000931284.1		c.492-21C>A		intron	N/A	ENSP00000601343.1

Frequencies

GnomAD3 genomes AF: 0.0401 AC: 6105 AN: 152064 Hom.: 159 Cov.: 33

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0505

Gnomad EAS AF: 0.0782

Gnomad SAS AF: 0.0320

Gnomad FIN AF: 0.0422

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0510

Gnomad OTH AF: 0.0374

GnomAD2 exomes AF: 0.0460 AC: 11541 AN: 251068 AF XY: 0.0471

Gnomad AFR exome AF: 0.0187

Gnomad AMR exome AF: 0.0209

Gnomad ASJ exome AF: 0.0548

Gnomad EAS exome AF: 0.0694

Gnomad FIN exome AF: 0.0484

Gnomad NFE exome AF: 0.0542

Gnomad OTH exome AF: 0.0487

GnomAD4 exome AF: 0.0527 AC: 76740 AN: 1456180 Hom.: 2285 Cov.: 28 AF XY: 0.0522 AC XY: 37863 AN XY: 724778

African (AFR) AF: 0.0183 AC: 610 AN: 33396

American (AMR) AF: 0.0219 AC: 978 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.0537 AC: 1399 AN: 26068

East Asian (EAS) AF: 0.0872 AC: 3453 AN: 39596

South Asian (SAS) AF: 0.0377 AC: 3249 AN: 86106

European-Finnish (FIN) AF: 0.0523 AC: 2788 AN: 53304

Middle Eastern (MID) AF: 0.0502 AC: 289 AN: 5760

European-Non Finnish (NFE) AF: 0.0550 AC: 60875 AN: 1107130

Other (OTH) AF: 0.0515 AC: 3099 AN: 60168

GnomAD4 genome AF: 0.0401 AC: 6104 AN: 152182 Hom.: 159 Cov.: 33 AF XY: 0.0387 AC XY: 2881 AN XY: 74396

African (AFR) AF: 0.0200 AC: 832 AN: 41536

American (AMR) AF: 0.0320 AC: 489 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0505 AC: 175 AN: 3468

East Asian (EAS) AF: 0.0780 AC: 405 AN: 5190

South Asian (SAS) AF: 0.0322 AC: 155 AN: 4816

European-Finnish (FIN) AF: 0.0422 AC: 446 AN: 10580

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0510 AC: 3468 AN: 68008

Other (OTH) AF: 0.0384 AC: 81 AN: 2110

Alfa AF: 0.0367 Hom.: 40

Bravo AF: 0.0386

Asia WGS AF: 0.0660 AC: 229 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	-0.81
CADD	Benign	6.5
DANN	Benign	0.72
PhyloP100		-0.0070
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs75016149; hg19: chr3-196022961; COSMIC: COSV57489067; COSMIC: COSV57489067;