chr2-210298339-T-TACACACAC

Variant names:

• chr2-210298339-T-TACACACAC
• rs112894708
• NM_079420.3:c.304+73_304+80dupGTGTGTGT

Variant summary

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

The NM_079420.3(MYL1):​c.304+73_304+80dupGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,179,084 control chromosomes in the GnomAD database, including 3,405 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1769 hom., cov: 0)
  • Exomes 𝑓: 0.13 (1636 hom.)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.73
• Publications: 0 publications found

Genes affected

MYL1 (HGNC:7582): (myosin light chain 1) Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene encodes a myosin alkali light chain expressed in fast skeletal muscle. Two transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

MYL1 Gene-Disease associations (from GenCC):

• congenital myopathy with reduced type 2 muscle fibers

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital myopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000279317 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 2-210298339-T-TACACACAC is Benign according to our data. Variant chr2-210298339-T-TACACACAC is described in ClinVar as Benign. ClinVar VariationId is 1253918.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_079420.3. 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
	MYL1	NM_079420.3	MANE Select	c.304+73_304+80dupGTGTGTGT		intron	N/A	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.172+73_172+80dupGTGTGTGT		intron	N/A	NP_524146.1	P05976-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL1	ENST00000352451.4	TSL:1 MANE Select	c.304+80_304+81insGTGTGTGT		intron	N/A	ENSP00000307280.4	P05976-1
	MYL1	ENST00000341685.8	TSL:1	c.172+80_172+81insGTGTGTGT		intron	N/A	ENSP00000343321.4	P05976-2
	MYL1	ENST00000957378.1		c.268+80_268+81insGTGTGTGT		intron	N/A	ENSP00000627437.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21339 AN: 147152 Hom.: 1766 Cov.: 0

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.110

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.128 AC: 132537 AN: 1031824 Hom.: 1636 AF XY: 0.128 AC XY: 67252 AN XY: 525956

African (AFR) AF: 0.0539 AC: 1410 AN: 26170

American (AMR) AF: 0.242 AC: 10036 AN: 41440

Ashkenazi Jewish (ASJ) AF: 0.0996 AC: 2095 AN: 21026

East Asian (EAS) AF: 0.200 AC: 7027 AN: 35174

South Asian (SAS) AF: 0.118 AC: 8372 AN: 71044

European-Finnish (FIN) AF: 0.163 AC: 7212 AN: 44176

Middle Eastern (MID) AF: 0.104 AC: 408 AN: 3934

European-Non Finnish (NFE) AF: 0.121 AC: 90148 AN: 743346

Other (OTH) AF: 0.128 AC: 5829 AN: 45514

GnomAD4 genome AF: 0.145 AC: 21357 AN: 147260 Hom.: 1769 Cov.: 0 AF XY: 0.150 AC XY: 10705 AN XY: 71556

African (AFR) AF: 0.0680 AC: 2707 AN: 39826

American (AMR) AF: 0.241 AC: 3539 AN: 14704

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 411 AN: 3428

East Asian (EAS) AF: 0.217 AC: 1056 AN: 4868

South Asian (SAS) AF: 0.139 AC: 629 AN: 4514

European-Finnish (FIN) AF: 0.203 AC: 1993 AN: 9822

Middle Eastern (MID) AF: 0.118 AC: 34 AN: 288

European-Non Finnish (NFE) AF: 0.154 AC: 10316 AN: 66872

Other (OTH) AF: 0.156 AC: 318 AN: 2044

Alfa AF: 0.141 Hom.: 299

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs112894708; hg19: chr2-211163063;