rs751040664

Variant names:

• chr3-196291390-AAC-A
• rs751040664
• NM_152773.5:c.382-18_382-17delGT

Your query was ambiguous. Multiple possible variants found:

• chr3-196291390-AAC-A
• chr3-196291390-AAC-AACAC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_152773.5(DYNLT2B):​c.382-18_382-17delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,605,408 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: DYNLT2B NM_152773.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.70
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 3-196291390-AAC-A is Benign according to our data. Variant chr3-196291390-AAC-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1914406.Status of the report is criteria_provided_single_submitter, 1 stars.

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.382-18_382-17delGT		intron	N/A	NP_689986.2	Q8WW35
	DYNLT2B	NM_001351628.2		c.382-23_382-22delGT		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.382-18_382-17delGT		intron	N/A	ENSP00000324323.5	Q8WW35
	ENSG00000272741	ENST00000431391.1	TSL:5	n.317+15551_317+15552delGT		intron	N/A	ENSP00000405181.1	E7ESA3
	DYNLT2B	ENST00000931284.1		c.556-18_556-17delGT		intron	N/A	ENSP00000601343.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000264 AC: 63 AN: 238422 AF XY: 0.000232

Gnomad AFR exome AF: 0.000261

Gnomad AMR exome AF: 0.000447

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.000406

Gnomad FIN exome AF: 0.0000933

Gnomad NFE exome AF: 0.000155

Gnomad OTH exome AF: 0.000354

GnomAD4 exome AF: 0.000145 AC: 211 AN: 1453288 Hom.: 0 AF XY: 0.000144 AC XY: 104 AN XY: 722862

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000121 AC: 4 AN: 33164

American (AMR) AF: 0.000251 AC: 11 AN: 43770

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 25980

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39298

South Asian (SAS) AF: 0.000236 AC: 20 AN: 84834

European-Finnish (FIN) AF: 0.0000563 AC: 3 AN: 53274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.000145 AC: 161 AN: 1107212

Other (OTH) AF: 0.0000833 AC: 5 AN: 60020

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74312

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000651 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs751040664; hg19: chr3-196018261; COSMIC: COSV53055974; COSMIC: COSV53055974;