NM_001372106.1:c.621+9G>A

Variant names:

• chr12-123774273-G-A
• rs202082455
• NM_001372106.1:c.621+9G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001372106.1(DNAH10):​c.621+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,557,024 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00063 (6 hom.)
• Consequence: DNAH10 NM_001372106.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

Genes affected

DNAH10 (HGNC:2941): (dynein axonemal heavy chain 10) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH10 is an inner arm dynein heavy chain (Maiti et al., 2000 [PubMed 11175280]).[supplied by OMIM, Mar 2008]

DNAH10 Gene-Disease associations (from GenCC):

• spermatogenic failure 56

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

LOC105370044 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-123774273-G-A is Benign according to our data. Variant chr12-123774273-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 708810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372106.1. 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
	DNAH10	NM_001372106.1	MANE Select	c.621+9G>A		intron	N/A	NP_001359035.1	A0A669KB38
	DNAH10	NM_207437.3		c.438+9G>A		intron	N/A	NP_997320.2	B0I1S1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	ENST00000673944.1	MANE Select	c.621+9G>A		intron	N/A	ENSP00000501095.1	A0A669KB38
	DNAH10	ENST00000409039.8	TSL:5	c.621+9G>A		intron	N/A	ENSP00000386770.4	A0A1C7CYW8
	DNAH10	ENST00000638045.1	TSL:5	c.438+9G>A		intron	N/A	ENSP00000489675.1	Q8IVF4-1

Frequencies

GnomAD3 genomes AF: 0.00449 AC: 684 AN: 152212 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00141 AC: 308 AN: 217868 AF XY: 0.00107

Gnomad AFR exome AF: 0.0131

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00580

Gnomad EAS exome AF: 0.000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000144

Gnomad OTH exome AF: 0.000982

GnomAD4 exome AF: 0.000626 AC: 880 AN: 1404694 Hom.: 6 Cov.: 23 AF XY: 0.000568 AC XY: 397 AN XY: 699490

African (AFR) AF: 0.0144 AC: 448 AN: 31110

American (AMR) AF: 0.00174 AC: 61 AN: 35046

Ashkenazi Jewish (ASJ) AF: 0.00508 AC: 123 AN: 24196

East Asian (EAS) AF: 0.000281 AC: 11 AN: 39180

South Asian (SAS) AF: 0.0000376 AC: 3 AN: 79882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52702

Middle Eastern (MID) AF: 0.00180 AC: 10 AN: 5554

European-Non Finnish (NFE) AF: 0.000133 AC: 143 AN: 1079048

Other (OTH) AF: 0.00140 AC: 81 AN: 57976

GnomAD4 genome AF: 0.00449 AC: 684 AN: 152330 Hom.: 1 Cov.: 33 AF XY: 0.00405 AC XY: 302 AN XY: 74496

African (AFR) AF: 0.0146 AC: 607 AN: 41566

American (AMR) AF: 0.00281 AC: 43 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68034

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00347 Hom.: 2

Bravo AF: 0.00523

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DNAH10-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.51
PhyloP100		1.2
Mutation Taster		=97/3	polymorphism

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: rs202082455; hg19: chr12-124258820;