rs1565817

Variant names:

• chr17-7797394-C-T
• rs1565817
• NM_020877.5:c.7950-6C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7797394-C-T
• chr17-7797394-C-A
• chr17-7797394-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020877.5(DNAH2):​c.7950-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 1,613,764 control chromosomes in the GnomAD database, including 307,714 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (23875 hom., cov: 31)
  • Exomes 𝑓: 0.62 (283839 hom.)
• Consequence: DNAH2 NM_020877.5 splice_region, intron
• Scores: Splicing: ADA: 0.0001956
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.01
• Publications: 17 publications found

Genes affected

DNAH2 (HGNC:2948): (dynein axonemal heavy chain 2) 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. DNAH2 is an axonemal inner arm dynein heavy chain (Chapelin et al., 1997 [PubMed 9256245]).[supplied by OMIM, Mar 2008]

DNAH2 Gene-Disease associations (from GenCC):

• spermatogenic failure 45

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 17-7797394-C-T is Benign according to our data. Variant chr17-7797394-C-T is described in ClinVar as Benign. ClinVar VariationId is 402710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020877.5. 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
	DNAH2	NM_020877.5	MANE Select	c.7950-6C>T		splice_region intron	N/A	NP_065928.2	Q9P225-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH2	ENST00000572933.6	TSL:2 MANE Select	c.7950-6C>T		splice_region intron	N/A	ENSP00000458355.1	Q9P225-1
	DNAH2	ENST00000389173.6	TSL:2	c.7950-6C>T		splice_region intron	N/A	ENSP00000373825.2	Q9P225-1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82263 AN: 151872 Hom.: 23865 Cov.: 31

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.558

GnomAD2 exomes AF: 0.612 AC: 153822 AN: 251384 AF XY: 0.613

Gnomad AFR exome AF: 0.309

Gnomad AMR exome AF: 0.701

Gnomad ASJ exome AF: 0.586

Gnomad EAS exome AF: 0.633

Gnomad FIN exome AF: 0.639

Gnomad NFE exome AF: 0.622

Gnomad OTH exome AF: 0.602

GnomAD4 exome AF: 0.620 AC: 906534 AN: 1461774 Hom.: 283839 Cov.: 64 AF XY: 0.620 AC XY: 450713 AN XY: 727194

African (AFR) AF: 0.304 AC: 10164 AN: 33480

American (AMR) AF: 0.696 AC: 31142 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 15175 AN: 26134

East Asian (EAS) AF: 0.604 AC: 23995 AN: 39700

South Asian (SAS) AF: 0.614 AC: 53003 AN: 86254

European-Finnish (FIN) AF: 0.645 AC: 34401 AN: 53370

Middle Eastern (MID) AF: 0.490 AC: 2826 AN: 5768

European-Non Finnish (NFE) AF: 0.629 AC: 699282 AN: 1111954

Other (OTH) AF: 0.605 AC: 36546 AN: 60392

GnomAD4 genome AF: 0.541 AC: 82294 AN: 151990 Hom.: 23875 Cov.: 31 AF XY: 0.548 AC XY: 40665 AN XY: 74270

African (AFR) AF: 0.315 AC: 13060 AN: 41456

American (AMR) AF: 0.635 AC: 9693 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2036 AN: 3464

East Asian (EAS) AF: 0.625 AC: 3233 AN: 5170

South Asian (SAS) AF: 0.619 AC: 2983 AN: 4818

European-Finnish (FIN) AF: 0.646 AC: 6813 AN: 10546

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42545 AN: 67970

Other (OTH) AF: 0.557 AC: 1172 AN: 2104

Alfa AF: 0.586 Hom.: 42824

Bravo AF: 0.532

Asia WGS AF: 0.618 AC: 2146 AN: 3478

EpiCase AF: 0.608

EpiControl AF: 0.607

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	DNAH2-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.57
PhyloP100		1.0
Mutation Taster		=83/17	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00020
dbscSNV1_RF	Benign	0.024
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: -8

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1565817; hg19: chr17-7700712; COSMIC: COSV66719970;