2-195897767-TAAAAAAAA-TAAAAAAAAAAAAA

Variant names:

• chr2-195897767-T-TAAAAA
• rs61502519
• NM_018897.3:c.4549-7_4549-3dupTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018897.3(DNAH7):​c.4549-7_4549-3dupTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: DNAH7 NM_018897.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 1 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.4549-7_4549-3dupTTTTT		splice_region intron	N/A	NP_061720.2

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome AF: 0.0000255 AC: 26 AN: 1020776 Hom.: 0 Cov.: 0 AF XY: 0.0000155 AC XY: 8 AN XY: 516100

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

African (AFR) AF: 0.00 AC: 0 AN: 22392

American (AMR) AF: 0.0000426 AC: 1 AN: 23476

Ashkenazi Jewish (ASJ) AF: 0.0000517 AC: 1 AN: 19332

East Asian (EAS) AF: 0.0000300 AC: 1 AN: 33324

South Asian (SAS) AF: 0.00 AC: 0 AN: 57658

European-Finnish (FIN) AF: 0.0000246 AC: 1 AN: 40654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4352

European-Non Finnish (NFE) AF: 0.0000258 AC: 20 AN: 775498

Other (OTH) AF: 0.0000454 AC: 2 AN: 44090

⚠️ 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 Cov.: 16

Alfa AF: 0.0000913 Hom.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs61502519; hg19: chr2-196762491;