Genetic Variant NM_002473.6:c.612+79C>T (chr22-36326489-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002473.6(MYH9):c.612+79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,277,416 control chromosomes in the GnomAD database, including 622,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 73742 hom., cov: 34)

Exomes 𝑓: 0.99 ( 548917 hom. )

Consequence

MYH9
NM_002473.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.525

Variant links:

Genes affected

MYH9 (HGNC:7579): (myosin heavy chain 9) This gene encodes a conventional non-muscle myosin; this protein should not be confused with the unconventional myosin-9a or 9b (MYO9A or MYO9B). The encoded protein is a myosin IIA heavy chain that contains an IQ domain and a myosin head-like domain which is involved in several important functions, including cytokinesis, cell motility and maintenance of cell shape. Defects in this gene have been associated with non-syndromic sensorineural deafness autosomal dominant type 17, Epstein syndrome, Alport syndrome with macrothrombocytopenia, Sebastian syndrome, Fechtner syndrome and macrothrombocytopenia with progressive sensorineural deafness. [provided by RefSeq, Dec 2011]

MYH9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 22-36326489-G-A is Benign according to our data. Variant chr22-36326489-G-A is described in ClinVar as [Benign]. Clinvar id is 1291297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6 link	c.612+79C>T		intron_variant	Intron 5 of 40	ENST00000216181.11	NP_002464.1	P35579-1A0A024R1N1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11 link	c.612+79C>T		intron_variant	Intron 5 of 40	1	NM_002473.6	ENSP00000216181.6		P35579-1

Frequencies

GnomAD3 genomes

AF:

0.984

AC:

149779

AN:

152254

Hom.:

73683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.971

Gnomad AMI

AF:

0.997

Gnomad AMR

AF:

0.987

Gnomad ASJ

AF:

0.973

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.991

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

0.953

Gnomad NFE

AF:

0.987

Gnomad OTH

AF:

0.983

GnomAD4 exome

AF:

0.988

AC:

1111304

AN:

1125044

Hom.:

548917

AF XY:

0.988

AC XY:

568618

AN XY:

575612

show subpopulations

Gnomad4 AFR exome

AF:

0.971

Gnomad4 AMR exome

AF:

0.992

Gnomad4 ASJ exome

AF:

0.975

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.992

Gnomad4 FIN exome

AF:

0.997

Gnomad4 NFE exome

AF:

0.987

Gnomad4 OTH exome

AF:

0.986

GnomAD4 genome

AF:

0.984

AC:

149897

AN:

152372

Hom.:

73742

Cov.:

AF XY:

0.984

AC XY:

73334

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.971

Gnomad4 AMR

AF:

0.988

Gnomad4 ASJ

AF:

0.973

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.991

Gnomad4 FIN

AF:

0.998

Gnomad4 NFE

AF:

0.987

Gnomad4 OTH

AF:

0.983

Alfa

AF:

0.985

Hom.:

19073

Bravo

AF:

0.983

Asia WGS

AF:

0.992

AC:

3449

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 90% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 84. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.34

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over