Genetic Variant DNAH7:c.4549-5_4549-3dupTTT (chr2-195897767-T-TAAA) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_018897.3(DNAH7):c.4549-5_4549-3dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000024 ( 0 hom., cov: 16)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

DNAH7
NM_018897.3 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.179

Publications

1 publications found

Variant links:

Genes affected

DNAH7 (HGNC:18661): (dynein axonemal heavy chain 7) DNAH7 is a component of the inner dynein arm of ciliary axonemes (Zhang et al., 2002 [PubMed 11877439]).[supplied by OMIM, Mar 2008]

DNAH7 Gene-Disease associations (from GenCC):

ciliary dyskinesia, primary, 50
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: LIMITED Submitted by: King Faisal Specialist Hospital and Research Center

DNAH7 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_018897.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP6

Variant 2-195897767-T-TAAA is Benign according to our data. Variant chr2-195897767-T-TAAA is described in ClinVar as Likely_benign. ClinVar VariationId is 3048456.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018897.3. 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
	DNAH7	NM_018897.3	MANE Select	c.4549-5_4549-3dupTTT		splice_region intron	N/A	NP_061720.2	Q8WXX0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	ENST00000312428.11	TSL:1 MANE Select	c.4549-3_4549-2insTTT		splice_region intron	N/A	ENSP00000311273.6	Q8WXX0-1
	DNAH7	ENST00000475293.1	TSL:1	n.5482-3_5482-2insTTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000240

AC:

AN:

124992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000833

Gnomad ASJ

AF:

0.000335

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000152

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00216

AC:

201

AN:

93048

AF XY:

0.00210

show subpopulations

Gnomad AFR exome

AF:

0.00165

Gnomad AMR exome

AF:

0.00357

Gnomad ASJ exome

AF:

0.00131

Gnomad EAS exome

AF:

0.00389

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.00186

Gnomad OTH exome

AF:

0.00177

GnomAD4 exome

AF:

0.00109

AC:

1114

AN:

1018680

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

567

AN XY:

515010

show subpopulations

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

African (AFR)

AF:

0.000939

AC:

AN:

22368

American (AMR)

AF:

0.00299

AC:

AN:

23404

Ashkenazi Jewish (ASJ)

AF:

0.00114

AC:

AN:

19280

East Asian (EAS)

AF:

0.00156

AC:

AN:

33234

South Asian (SAS)

AF:

0.00270

AC:

155

AN:

57442

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

40592

Middle Eastern (MID)

AF:

0.000690

AC:

AN:

4348

European-Non Finnish (NFE)

AF:

0.000908

AC:

703

AN:

773988

Other (OTH)

AF:

0.000954

AC:

AN:

44024

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.274

Heterozygous variant carriers

112

224

335

447

559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000240

AC:

AN:

124992

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

59848

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

36860

American (AMR)

AF:

0.0000833

AC:

AN:

11998

Ashkenazi Jewish (ASJ)

AF:

0.000335

AC:

AN:

2982

East Asian (EAS)

AF:

0.00

AC:

AN:

3974

South Asian (SAS)

AF:

0.00

AC:

AN:

3744

European-Finnish (FIN)

AF:

0.000152

AC:

AN:

6574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

56238

Other (OTH)

AF:

0.00

AC:

AN:

1680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

DNAH7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.18

Mutation Taster

=88/12

polymorphism

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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2-195897767-TAAAAAAAA-TAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over