rs763561186

Variant names:

• chr14-101964904-C-T
• rs763561186
• NM_001376.5:c.213C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-101964904-C-T
• chr14-101964904-C-A
• chr14-101964904-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001376.5(DYNC1H1):​c.213C>T​(p.Asp71Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,448,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: DYNC1H1 NM_001376.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.738
• Publications: 0 publications found

Genes affected

DYNC1H1 (HGNC:2961): (dynein cytoplasmic 1 heavy chain 1) 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 member of the cytoplasmic dynein heavy chain family. [provided by RefSeq, Oct 2008]

DYNC1H1 Gene-Disease associations (from GenCC):

• autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P
• intellectual disability, autosomal dominant 13

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• neuronopathy, distal hereditary motor

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease axonal type 2O

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 14-101964904-C-T is Benign according to our data. Variant chr14-101964904-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 539826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.738 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000018 (26/1448104) while in subpopulation AFR AF = 0.0000301 (1/33276). AF 95% confidence interval is 0.0000147. There are 0 homozygotes in GnomAdExome4. There are 13 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 26 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376.5. 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
	DYNC1H1	NM_001376.5	MANE Select	c.213C>T	p.Asp71Asp	synonymous	Exon 1 of 78	NP_001367.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC1H1	ENST00000360184.10	TSL:1 MANE Select	c.213C>T	p.Asp71Asp	synonymous	Exon 1 of 78	ENSP00000348965.4	Q14204
	DYNC1H1	ENST00000681574.1		c.213C>T	p.Asp71Asp	synonymous	Exon 1 of 77	ENSP00000505523.1	A0A7P0T9C4
	DYNC1H1	ENST00000679720.1		c.213C>T	p.Asp71Asp	synonymous	Exon 1 of 78	ENSP00000505938.1	A0A7P0TA13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000897 AC: 2 AN: 222926 AF XY: 0.0000164

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000101

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000180 AC: 26 AN: 1448104 Hom.: 0 Cov.: 31 AF XY: 0.0000181 AC XY: 13 AN XY: 719260

African (AFR) AF: 0.0000301 AC: 1 AN: 33276

American (AMR) AF: 0.00 AC: 0 AN: 42904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25766

East Asian (EAS) AF: 0.00 AC: 0 AN: 39300

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4576

European-Non Finnish (NFE) AF: 0.0000217 AC: 24 AN: 1106700

Other (OTH) AF: 0.00 AC: 0 AN: 59754

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Charcot-Marie-Tooth disease axonal type 2O (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.96
PhyloP100		0.74
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs763561186; hg19: chr14-102431241;