2-195897767-TAAAAAAAA-TAAAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018897.3(DNAH7):​c.4549-3delT 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. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (6370 hom., cov: 16)
  • Exomes 𝑓: 0.29 (358 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAH7 NM_018897.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 2-195897767-TA-T is Benign according to our data. Variant chr2-195897767-TA-T is described in ClinVar as Benign. ClinVar VariationId is 402752.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

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.4549-3delT		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.4549-3delT		splice_region intron	N/A	ENSP00000311273.6	Q8WXX0-1
	DNAH7	ENST00000475293.1	TSL:1	n.5482-3delT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.291 AC: 36335 AN: 124844 Hom.: 6361 Cov.: 16

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0103

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.211

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.286

GnomAD2 exomes AF: 0.369 AC: 34356 AN: 93048 AF XY: 0.369

Gnomad AFR exome AF: 0.409

Gnomad AMR exome AF: 0.332

Gnomad ASJ exome AF: 0.373

Gnomad EAS exome AF: 0.320

Gnomad FIN exome AF: 0.364

Gnomad NFE exome AF: 0.382

Gnomad OTH exome AF: 0.348

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.294 AC: 290269 AN: 988694 Hom.: 358 Cov.: 0 AF XY: 0.294 AC XY: 146773 AN XY: 498868

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

African (AFR) AF: 0.402 AC: 8881 AN: 22078

American (AMR) AF: 0.283 AC: 6412 AN: 22662

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 5751 AN: 18550

East Asian (EAS) AF: 0.249 AC: 7612 AN: 30582

South Asian (SAS) AF: 0.261 AC: 14624 AN: 56008

European-Finnish (FIN) AF: 0.288 AC: 11024 AN: 38258

Middle Eastern (MID) AF: 0.340 AC: 1434 AN: 4212

European-Non Finnish (NFE) AF: 0.294 AC: 221831 AN: 753830

Other (OTH) AF: 0.299 AC: 12700 AN: 42514

⚠️ 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: 0.291 AC: 36367 AN: 124856 Hom.: 6370 Cov.: 16 AF XY: 0.285 AC XY: 17057 AN XY: 59806

African (AFR) AF: 0.535 AC: 19715 AN: 36878

American (AMR) AF: 0.195 AC: 2342 AN: 11996

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 697 AN: 2982

East Asian (EAS) AF: 0.0106 AC: 42 AN: 3952

South Asian (SAS) AF: 0.132 AC: 488 AN: 3706

European-Finnish (FIN) AF: 0.150 AC: 982 AN: 6544

Middle Eastern (MID) AF: 0.203 AC: 43 AN: 212

European-Non Finnish (NFE) AF: 0.204 AC: 11455 AN: 56186

Other (OTH) AF: 0.289 AC: 488 AN: 1688

Alfa AF: 0.0310 Hom.: 16

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18
Mutation Taster		=99/1	polymorphism (auto)

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

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

Other links and lift over

dbSNP: rs61502519;

hg19: chr2-196762491;

COSMIC: COSV56749777;