2-195897767-TAAAAAAAA-TAAAAAAAAA

Variant names:

• chr2-195897767-T-TA
• rs61502519
• NM_018897.3:c.4549-3dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_018897.3(DNAH7):​c.4549-3dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (29 hom., cov: 16)
  • Exomes 𝑓: 0.13 (1 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0162 (2029/124950) while in subpopulation AMR AF = 0.0375 (450/11998). AF 95% confidence interval is 0.0346. There are 29 homozygotes in GnomAd4. There are 978 alleles in the male GnomAd4 subpopulation. Median coverage is 16. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

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.4549-3dupT		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_4549-2insT		splice_region intron	N/A	ENSP00000311273.6
	DNAH7	ENST00000475293.1	TSL:1	n.5482-3_5482-2insT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2026 AN: 124940 Hom.: 29 Cov.: 16

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.00402

Gnomad EAS AF: 0.00554

Gnomad SAS AF: 0.00374

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.00435

Gnomad NFE AF: 0.00640

Gnomad OTH AF: 0.0161

GnomAD2 exomes AF: 0.0945 AC: 8789 AN: 93048 AF XY: 0.0931

Gnomad AFR exome AF: 0.0590

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.0984

Gnomad EAS exome AF: 0.145

Gnomad FIN exome AF: 0.0910

Gnomad NFE exome AF: 0.0832

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.126 AC: 125904 AN: 1001922 Hom.: 1 Cov.: 0 AF XY: 0.126 AC XY: 63620 AN XY: 506304

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

African (AFR) AF: 0.0674 AC: 1490 AN: 22094

American (AMR) AF: 0.136 AC: 3129 AN: 23054

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2128 AN: 18888

East Asian (EAS) AF: 0.160 AC: 5120 AN: 32092

South Asian (SAS) AF: 0.145 AC: 8216 AN: 56534

European-Finnish (FIN) AF: 0.120 AC: 4753 AN: 39614

Middle Eastern (MID) AF: 0.0922 AC: 394 AN: 4274

European-Non Finnish (NFE) AF: 0.125 AC: 95262 AN: 762162

Other (OTH) AF: 0.125 AC: 5412 AN: 43210

⚠️ 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: 0.0162 AC: 2029 AN: 124950 Hom.: 29 Cov.: 16 AF XY: 0.0163 AC XY: 978 AN XY: 59856

African (AFR) AF: 0.0284 AC: 1047 AN: 36906

American (AMR) AF: 0.0375 AC: 450 AN: 11998

Ashkenazi Jewish (ASJ) AF: 0.00402 AC: 12 AN: 2982

East Asian (EAS) AF: 0.00556 AC: 22 AN: 3954

South Asian (SAS) AF: 0.00377 AC: 14 AN: 3714

European-Finnish (FIN) AF: 0.0146 AC: 96 AN: 6560

Middle Eastern (MID) AF: 0.00467 AC: 1 AN: 214

European-Non Finnish (NFE) AF: 0.00640 AC: 360 AN: 56220

Other (OTH) AF: 0.0160 AC: 27 AN: 1690

Alfa AF: 0.000639 Hom.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18
Mutation Taster		=93/7	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: rs61502519; hg19: chr2-196762491;