2-195897767-TAAAAAAAA-TAAAAAA

Variant names:

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

Variant summary

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

The NM_018897.3(DNAH7):​c.4549-4_4549-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 1,116,596 control chromosomes in the GnomAD database, including 5 homozygotes. 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 0.0042 (5 hom., cov: 16)
  • Exomes 𝑓: 0.032 (0 hom.)
• Consequence: DNAH7 NM_018897.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• 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 afr. GnomAd4 allele frequency = 0.00419 (523/124966) while in subpopulation AFR AF = 0.0123 (453/36912). AF 95% confidence interval is 0.0113. There are 5 homozygotes in GnomAd4. There are 257 alleles in the male GnomAd4 subpopulation. Median coverage is 16. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 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.4549-4_4549-3delTT		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.4549-4_4549-3delTT		splice_region intron	N/A	ENSP00000311273.6
	DNAH7	ENST00000475293.1	TSL:1	n.5482-4_5482-3delTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00419 AC: 523 AN: 124956 Hom.: 5 Cov.: 16

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00233

Gnomad ASJ AF: 0.00101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000534

Gnomad FIN AF: 0.00168

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000356

Gnomad OTH AF: 0.00357

GnomAD2 exomes AF: 0.0485 AC: 4517 AN: 93048 AF XY: 0.0494

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.0472

Gnomad ASJ exome AF: 0.0476

Gnomad EAS exome AF: 0.0280

Gnomad FIN exome AF: 0.0240

Gnomad NFE exome AF: 0.0478

Gnomad OTH exome AF: 0.0504

GnomAD4 exome AF: 0.0317 AC: 31412 AN: 991630 Hom.: 0 AF XY: 0.0320 AC XY: 16037 AN XY: 501208

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

African (AFR) AF: 0.0827 AC: 1808 AN: 21868

American (AMR) AF: 0.0399 AC: 902 AN: 22598

Ashkenazi Jewish (ASJ) AF: 0.0374 AC: 701 AN: 18732

East Asian (EAS) AF: 0.0162 AC: 519 AN: 31962

South Asian (SAS) AF: 0.0363 AC: 2026 AN: 55862

European-Finnish (FIN) AF: 0.0243 AC: 957 AN: 39370

Middle Eastern (MID) AF: 0.0308 AC: 131 AN: 4250

European-Non Finnish (NFE) AF: 0.0304 AC: 22937 AN: 754260

Other (OTH) AF: 0.0335 AC: 1431 AN: 42728

⚠️ 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: 0.00419 AC: 523 AN: 124966 Hom.: 5 Cov.: 16 AF XY: 0.00429 AC XY: 257 AN XY: 59854

African (AFR) AF: 0.0123 AC: 453 AN: 36912

American (AMR) AF: 0.00233 AC: 28 AN: 12010

Ashkenazi Jewish (ASJ) AF: 0.00101 AC: 3 AN: 2980

East Asian (EAS) AF: 0.00 AC: 0 AN: 3954

South Asian (SAS) AF: 0.000539 AC: 2 AN: 3714

European-Finnish (FIN) AF: 0.00168 AC: 11 AN: 6560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.000356 AC: 20 AN: 56220

Other (OTH) AF: 0.00355 AC: 6 AN: 1690

Alfa AF: 0.00 Hom.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=94/6	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; COSMIC: COSV56780692;