2-195897767-TAAAAAAAA-TAAAAAAAAAA

Variant names:

• chr2-195897767-T-TAA
• rs61502519
• NM_018897.3:c.4549-4_4549-3dupTT

Variant summary

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

The NM_018897.3(DNAH7):​c.4549-4_4549-3dupTT 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: 𝑓 0.00011 (0 hom., cov: 16)
  • Exomes 𝑓: 0.010 (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.4549-4_4549-3dupTT		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_4549-2insTT		splice_region intron	N/A	ENSP00000311273.6
	DNAH7	ENST00000475293.1	TSL:1	n.5482-3_5482-2insTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 14 AN: 124982 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.000109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000834

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000761

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000711

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0139 AC: 1289 AN: 93048 AF XY: 0.0131

Gnomad AFR exome AF: 0.00811

Gnomad AMR exome AF: 0.0221

Gnomad ASJ exome AF: 0.0118

Gnomad EAS exome AF: 0.0265

Gnomad FIN exome AF: 0.00637

Gnomad NFE exome AF: 0.0126

Gnomad OTH exome AF: 0.0181

GnomAD4 exome AF: 0.00998 AC: 10060 AN: 1008282 Hom.: 0 Cov.: 0 AF XY: 0.0101 AC XY: 5160 AN XY: 509836

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

African (AFR) AF: 0.00561 AC: 125 AN: 22262

American (AMR) AF: 0.0175 AC: 407 AN: 23192

Ashkenazi Jewish (ASJ) AF: 0.00983 AC: 188 AN: 19130

East Asian (EAS) AF: 0.0113 AC: 369 AN: 32788

South Asian (SAS) AF: 0.0185 AC: 1051 AN: 56758

European-Finnish (FIN) AF: 0.00932 AC: 375 AN: 40216

Middle Eastern (MID) AF: 0.00696 AC: 30 AN: 4312

European-Non Finnish (NFE) AF: 0.00925 AC: 7085 AN: 766054

Other (OTH) AF: 0.00987 AC: 430 AN: 43570

⚠️ 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 AF: 0.000112 AC: 14 AN: 124982 Hom.: 0 Cov.: 16 AF XY: 0.000150 AC XY: 9 AN XY: 59842

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

African (AFR) AF: 0.000109 AC: 4 AN: 36860

American (AMR) AF: 0.0000834 AC: 1 AN: 11996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2982

East Asian (EAS) AF: 0.00 AC: 0 AN: 3974

South Asian (SAS) AF: 0.00 AC: 0 AN: 3744

European-Finnish (FIN) AF: 0.000761 AC: 5 AN: 6568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 230

European-Non Finnish (NFE) AF: 0.0000711 AC: 4 AN: 56238

Other (OTH) AF: 0.00 AC: 0 AN: 1678

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000109461), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18
Mutation Taster		=88/12	polymorphism

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;